Neuronal Membrane Potentials Explained

What's up Ninja Nerds? In this video today we're going to talk about resting membrane potentials, graded potentials, and action potentials of neurons. Guys before you guys watch this video please hit that like button hit that subscribe button, comment down in the comment section, and all of the information for all our social media platforms, Instagram, Facebook, Patreon, all of that will be listed down in the description box. Go check that out. All right, let's go ahead and get started. All right, Ninjner, so what we have to do when we're talking about all of these membrane potentials within a neuron is we have to zoom in on the neuron, really talk about all that cellular processing and ion movement that is occurring here. So first thing we have to talk about, since we're talking about all these potentials of a neuron, we have to start with resting membrane potential. Now, first thing we have to do is come up with just a basic definition of resting membrane potential. So how would you describe resting membrane potential? What is it? Well, resting membrane potential is the voltage difference across this cell membrane when the cell is at rest. That's all it is. So it's the voltage difference across the cell, cell membrane. At rest. And the next thing that you have to remember is, is yes, we're talking about this resting membrane potential existing in neurons, but resting membrane potentials can exist in every single cell. So it exists in all cells. That's very important to remember. We're just referring to it in this case in the neurons. Okay. The next thing that you have to know is what is this actual wall. voltage, if we could put a value, a number on this voltage difference across the cell membrane at rest in a neuron, what would it be? And it's actually a range. So I'm going to abbreviate resting membrane potential. Generally, this is a range. Now, most textbooks like Marriott says it's around negative 70 millivolts. That's kind of like the average. Other textbooks will give it a little bit farther from that. The best way to kind of just cover all grounds is to say, generally, it could be somewhere between negative 70 millivolts to negative 90 millivolts with most textbooks supporting negative 70 millivolts is that kind of average number okay so that's kind of what we know about resting membrane potentials now what we need to do is I want you to understand what we're looking at because we're zooming in on a neuron so what I'm actually doing here is I'm taking a neuron right we're looking at a neuron like this all right here is going to be your axon your cell body And then here we're going to have the axon terminal. Okay. What I'm doing is I'm zooming in on this portion of the cell membrane and we're looking at that. Okay. That's what we're doing here. So we're really zooming in on the cell membrane of this neuron and looking at the activity. So you have to have one question here. How in the heck does your resting membrane potential get to negative 70 to negative 90 millivolts? How do we get it there? There's three ways that we get it there. One of the ways that we get it to that voltage, that negative 70 to negative 90, is sodium potassium ATPases. These sodium potassium ATPases, what they do is they're so interesting and they're so intelligent, and they pump three sodium ions out of the cell. So three cations or positive ions out of the cell. And then they pump two potassium ions or two cations into the cell. Now, take a look at this. Let's pretend for a second we're starting at a particular voltage. Let's say we're starting at zero millivolts. That's our imaginary start point of how we're going to get to negative 70 millivolts. So we're starting at zero millivolts. Now when these sodium potassium ATPases are working, they're pumping three positive ions out and only bringing two positive ions in. Because of that, that makes the inside of the cell just a little bit more negative. Not significant, just a teensy bit negative. Maybe it only takes it from 0 millivolts to negative 5 millivolts. So not a big change, but that's obviously due to the sodium potassium ATPases. So these are going to be one of the reasons, okay? So what are these called here? These are called your sodium potassium ATPases. Now, that's one function. One of the functions of the sodium potassium ATPases is... is to help to make the inside of the cell just slightly negative. The second reason that these are so important is that they establish the concentration gradient for sodium and potassium. Now, what is it doing to the sodium, these pumps? It's pushing sodium out. So what is that doing? That's increasing the concentration of sodium outside the cell. And by contrast, the sodium concentration inside of the cell will be lower. Okay? Now, It's also concentrating potassium into the cells, pushing lots of potassium in. So what that's going to do is that's going to increase the potassium concentration inside the cell. And in contrast, there'll be less potassium outside the cell. So there's two functions of these sodium potassium ATPases. One is they generate a small negative charge inside of the cell at rest. The second reason, the second thing that they do is they generate concentration gradient for these ions to move. And that's going to be important for the next two things. that contribute to the resting membrane potential. Okay beautiful. Now the second thing that contributes to the resting membrane potential are over here, these blue channels. Okay and that leads us to our next discussion. There's going to be lots of different channels within a neuron that contributes to all these different potentials, resting, graded, action. When we're talking about resting membrane potential, these blue channels here are very special types of channels. They are called leaky potassium channels and what that means is is that there are these little proteins embedded in the cell membrane and they're always open and they allow for ions like potassium in this case to move in and out of the cell freely and keyword here passively okay now these potassium channels are super leaky so that's gonna allow for ions like potassium to move which direction would the potassium want to move Well remember, what did we just say over here with the concentration gradients? Potassium is higher inside of the cell because of these sodium potassium ATPases. So if potassium is higher outside the cell and it's lower outside the cell, where is it going to want to go? It's going to want to leave this cell and exit. So all this potassium is going to start leaving the cell. So let's have this showing here that the potassium is leaving the cell and how is it leaving? It's leaving moving what? down its concentration gradient from high concentration to low concentration. From the intracellular fluid to the extracellular fluid. Okay, beautiful. Now, as these positive ions, these potassium ions are leaving, what's happening to the inside of the cell? Great question, guys. Potassium is actually bound normally inside of the cell. Potassium is bound to an anion. You see this? I'm going to represent it as A. Okay, A is just your non-specific anion, negatively charged ion. What are these anions and why am I mentioning it? These anions can be of two types, okay? These anions that I'm representing here as A-can be of two things. One is they can be phosphates. You know phosphates are just really negatively charged ions, very difficult for them to move outside of the cell because of that charge. The other thing, oh, let me get my marker here. The other thing here is going to be proteins. Proteins. You know proteins are made up of amino acids, right? Tons of amino acids. And these amino acids have lots of negative charges on them. Well, that's another reason they can't exit the cell. But what did I say was the common thing with these? This has negative charges. This has negative charges. That's what makes it an ion. They love to interact with potassium, which is a cation. So whenever potassium leaves, you would think, oh, the anion's also going to leave. No, it's too big and too charged to leave the cell. So because of that, whenever potassium leaves, it leaves behind an unoccupied anion. And now every time the potassium leaves, it leaves behind an unoccupied anion and makes the inside of the cell more and more and more negative. So now this is super negative inside of the cell. What? voltage you're not going to believe this but if potassium could it would move outside of the cell until you got that voltage somewhere around let's say negative 90 millivolts let's say that it took the inside of the cell and flipped it from negative five went all the way down to negative 90 millivolts that was because of these leaky potassium channels now the last one that contributes so we have the sodium potassium pumps The leaky potassium channels, the last one that is going to contribute here to this resting membrane potential is your leaky sodium channels. Now, remember, there is other ions that can move in and out of these cells, calcium, chloride. I'm only considering sodium and potassium to be the main ions because those are the ones that are the most significant in this case. But do realize I could consider calcium and chloride as well. But for right now, what I want you to remember is one is sodium potassium ATPases, second is leaky potassium channels, the third one here... is going to be the leaky sodium channels. Now these are leaky again they allow for sodium to move in or out of the cell. But again where is the concentration gradient of sodium? We already said it's higher outside the cell. So if the concentration of sodium is higher outside the cell, in contrast it's lower inside the cell. So where will the sodium want to move? The sodium will then want to move into the cell down its concentration gradient. As sodium moves into the cell, down its concentration gradient, it makes the inside of the cell positive. But here is the big thing, I can't stress this enough. This cell, in this case a neuron, is so many more times permeable to potassium than it is to sodium. It'll allow for tons and tons of potassium to leak out of the cell, but only allow a little bit of sodium to come into the cell. So because of that, we have to, let's actually write this down. That potassium, when we talk about permeability, we'll kind of put like a little heading here, permeability factors, right? When we're talking about that with the cell, potassium is significantly more permeable. This cell's way more permeable to potassium than it is to sodium. So potassium will make a big change, like go from negative five to negative 90, but the sodium, not much of it moves in. So because of that, it might not make as significant as a change. Maybe it only takes it from negative 90 to negative 70 millivolts. And we've reached our resting membrane potential. So to recap, what are the three components that are actually helping us with this? Sodium potassium ATPases, the leaky potassium channels, the leaky sodium channels. And if you really wanted to add other ones in, leaky calcium and leaky chloride channels. But the same concept applies. Last thing that we have to talk about this because this does come up on your exams a lot is learning how to calculate what's called the Nernst potential for sodium, potassium, calcium, chloride. We're literally just going to go through the equation quickly. All right. So when we talk about Nernst potential, really, I only want you to know the equation. And then really it's a plug and chug thing from here. There really isn't much to this. It's more important for you to know when you use the Nernst potential and what that Nernst potential like formula is. Okay, so NERF potential. The first thing that you need to know is when do you use it? So when do you use it? And that's a very important question. Let's take for example potassium in this case. Okay, potassium we know is moving out of the cell down its concentration gradient. But as it moves outside of the cell, the inside of the cell becomes positive. I'm sorry, becomes more negative, right? That negative charge inside the cell wants to pull some of the potassium back into the cell. That's called the electrostatic gradient. So potassium moves out of the cell down its concentration gradient, but kind of gets pulled back into the cell down its electrostatic gradient. The point in time in which potassium is moving equally, or there's kind of like no net movement of potassium moving out of the cell down its concentration gradient, or moving into the cell down its electrostatic gradient, whenever those two are equal, that movement, you've reached NERTS potential. So we kind of write it like this. Whenever the potassium is moving out of the cell equals the potassium moving into the cell. And moving out is via its concentration gradient, right? Its concentration gradient. And moving into the cell is via its electrostatic gradient. Then we can use the equation. Well, then the next question is what is the equation? That equation is like this. We're going to write it for potassium. E for voltage. Okay, the equilibrium or the voltage that potassium is able to generate across that cell membrane at rest is equal to 61.5, which is a constant divided by Z, which is just basically the charge of the ion. In this case, what's the charge of potassium? Plus one. What's 61.5 divided by plus one? 61.5. So we can just get rid of that. Multiply by... log base 10, the concentration of potassium ions outside of the cell. And again, this is a value that you would get from a table or a textbook. And we're going to put down here five is the potassium concentration outside the cell. So this is here, right? Another thing over here, there's the potassium concentration outside of the cell over the potassium concentration inside the cell. And again, this could be 150, right? If you calculate all of this out, That'll come somewhere around negative 90 millivolts. So that tells you that potassium will move outside of the cell until it'll move outside of the cell down its concentration gradient until the inside of the cell becomes negative 90 millivolts. And then that movement down its electrostatic gradient keeps it in that kind of equilibrium point. Now, the same concept goes for sodium. If I wanted to calculate for sodium, I'd say equilibrium potential of sodium is equal to 61.5 divided by Z. It's a plus 1, so I don't need to, times log base 10. And then again, I'd have to kind of pull this number from a table. And generally, that's like 140 for the sodium concentration outside of the cell, and then about 10 for the sodium concentration inside the cell. And then again, if you calculate all of this, you're going to get your equilibrium potential of sodium is somewhere around positive 70 millivolts. Now, if you added both of these up, negative 90 and positive 70, you're basically saying that your resting membrane potential is the equilibrium potential of potassium and the equilibrium potential of sodium. And if you did that, what would you get? Positive, you get negative 20 millivolts, negative 90 plus 70. But remember, what did I say? It's a permeability thing. So potassium, there's going to be so much more potassium moving out of the cell. So the cell voltage will actually be closer to this equilibrium potential of potassium. So whenever you actually calculate this out, if you were to take a percentage and say, well, let's say that this cell is 90% permeable to potassium and only 10% permeable to sodium. If you calculated all of this out and then added them together, you would probably get somewhere approximately around negative 70 millivolts. And that is kind of how we really get down into the nitty gritty of how to calculate out these voltages. All right. Good enough. Graded potentials. All right, guys. So we talked about resting membrane potentials. Okay. Now what we have to do is take that resting membrane potential, negative 70 millivolts we said about, right? How we figured that out we already talked about. Now what we got to do is we got to get that negative 70 millivolts to a threshold voltage. We're getting closer towards an action potential. We're building a story is what we're doing here. Okay. So now the purpose of graded potentials, the true underlying purpose, is to either take the resting membrane potential, right, and move it closer to threshold, right? So if you're trying to move it closer to threshold voltage, right, which is that voltage that we need to open up voltage-gated sodium channels in the axon, that threshold voltage is generally negative 55 millivolts, approximately. If I want to get my negative 70 millivolts to negative 55 millivolts, I need a slight depolarization, right? But you know what else? Sometimes we don't want to stimulate an axon. Sometimes we don't want to stimulate an action potential. So another aspect of graded potentials is not just depolarizing or bringing it to threshold, but sometimes we can take that resting membrane potential at negative 70 millivolts and actually take it away from threshold and maybe bring it even lower than resting membrane potential, right? And we could actually take this maybe down to negative 90 millivolts. This is called hyper polarizing okay you're hyper polarizing the cell you're making it even more negative there's particular names for these and that's what we really have to discuss whenever you take the resting membrane potential and you try to bring it to threshold you're trying to excite this cell this neuron and we give a term for this we call this an e p s p an excitatory post-synaptic potential But then if you have another neuron that you're actually trying to inhibit, taking it farther away from threshold. Now look how much farther away we are from threshold. We're at negative 90. It's going to be so hard to stimulate this neuron. So because of that, if you're really trying to inhibit this neuron, this is going to be called an IPSP, an inhibitory postsynaptic potential. Now, to give you an idea of what we're zooming in on and really looking at here, let's say we take another neuron. Here's our neuron, okay? And here, we're going to have another neuron. We're going to have one neuron over here acting on this guy, and then we'll have another neuron right here acting on this. What we're doing is, is we're zooming in right here and taking a look at this portion here. We're zooming in here on this cell membrane, and we're taking a look at how these neurons are influencing this postsynaptic neuron. So again terminology. These are called presynaptic neurons because this space here is called your synapse. This right here is After the synapse, so this is called your post synaptic neuron. So you have pre synaptic post synaptic neurons We're zooming in on that synapse. Okay, first thing that I want you to know We're gonna have to have something that excites the cell So what we're gonna do is we're gonna give a stimulatory signal here. We're gonna call this Neuron here this neuron that's gonna be trying this pre synaptic neuron is going to try to excite this cell this post synaptic neuron And the way it's gonna do it is it's gonna release a particular neurotransmitter Let's just pick, in this case, a stimulatory neurotransmitter like glutamate. You know, glutamate is a very good stimulator within the central nervous system. So what we're going to do is we're going to have glutamate bind onto this little receptor site. See how there's this little pocket there? That little pocket is important because once glutamate binds into it, normally what's happening is these channels are closed. And we have to talk about what type of channel this is. Normally there's like a little gate there blocking it, right? There's a little gate there blocking any ions from coming in. But once glutamate binds onto this little pocket, it lifts this gate up. And now what was closed over that kind of like porous surface is now opened up. Now look at the gate. It's popped up. And now what happens is this opens up the channel for ions to flow in. What kind of ions? Any type of cation generally. Maybe it's sodium that'll flow into this cell. Maybe it's calcium that'll flow into this cell. And as the sodium ions and the calcium ions start to move inside of the cell, it makes the inside of the cell positive. Well, remember, what was the voltage previously inside of the cell? We were at negative 70 millivolts. And now what's going to happen is that these positive ions moving into the cell are going to try to start moving the inside of the cell towards that positive range, more positive. Maybe negative 55 millivolts is what we want it to get to. Okay, that's what this EPSP means. It brings in positive ions into the cell. How does it do that? By the neurotransmitter glutamate binding to this type of channel. What is this channel here called? Whenever a ligand or neurotransmitter or chemical binds onto this pocket of this channel and opens it up. This is called, it goes by many names, but I like to refer to them as ligand gated ion. channel. Okay? Alright, beautiful. So these are your ligand-gated ion channels. And they're going to be one of the things, in this case, a stimulatory neurotransmitter bringing positive ions in. This is going to lead to this EPSP we talked about. And we'll represent this graphically in a second. On the other situation, we have to have the opposing action, the IPSPs. So now what we're going to do is we're going to have an inhibitory neurotransmitter here. And this inhibitory neurotransmitter is going to release a particular neurotransmitter that's commonly going to cause inhibition. What's this kind? This could be something like GABA, gamma-aminobutric acid. Gamma-aminobutric acid or GABA is actually going to bind onto this little pocket. And again, let's pretend that this little pocket had this gate closed, okay? But whenever GABA binds on, it stimulates this type of channel, and then what it does is it opens up. that little gate that was previously blocking the opening. And what this does is this allows for chloride ions to come into the cell. So now you have chloride ions coming into the cell. Or it can allow for potassium ions to leave the cell. Now if potassium ions leave the cell, what do they leave behind? Remember, what does potassium normally bound to? An anion. And these anions are proteins and phosphates and they can't leave the cell. So whenever potassium leaves, it leaves behind the... anion. And if you leave behind the anions, that makes the inside of the cell negative. If you bring chloride ions, which are negatively charged ions inside of the cell, what's that going to do? Make the inside of the cell negative. What was the previous voltage inside of the cell at rest before we even had this GABA acting on this ligand gated ion channel? It was negative 70 millivolts. What happened is, is you brought in all these negative ions. in the form of chloride or at potassium ions leave cations leaving that made the inside of the cell negative and it hyperpolarized it and took it from negative 70 to negative um 90 millivolts let's say okay so it made it even more negative that is called a ipsp now here's the thing This is a constant battle. There's a constant battle between this neuron. You can have multiple stimulatory and inhibitory signals acting on this one neuron. Your goal obviously is to have more EPSPs than IPSPs. But if you were to look at this in a graphical representation, on the x-axis we got time, milliseconds, and on the y-axis we've got millivolts. Let's say here is my resting membrane potential, right? What was that voltage we said? Negative 70 millivolts, right? What's my threshold? My threshold is negative 55 millivolts. That's where I want to get to so I can open up those voltage-gated sodium channels in the axon, trigger and action potential. So that's going to be this pink line. This is my threshold potential. How do we try to get there? EPSPs, right? This is what we want. We want stimulatory signals. We don't want as many inhibitory signals. But in life, that's not how everything always works. So sometimes what may happen is maybe you have an EPSP, right? And that EPSP is getting close to that threshold potential, but it's just not enough. If you don't hit the threshold potential, you don't get an action potential, right? It's kind of that all or none phenomenon. So maybe what happens is you get to this point and you try to trigger, right, this depolarization and it just doesn't get there. Okay. And then maybe what happens is you get another EPSP that fires. And maybe you just get a little bit closer, but you still don't hit that threshold potential. At the same time, you could also be having what else? You could also be having these IPSPs firing. They could also be trying to bring the voltage below, and then another one fires and brings it below. So it's a constant battle between these two. How could we ever get the EPSPs and IPSPs to get to this point where I can hit the threshold? The whole goal... is I need to have more EPSPs, right, than IPSPs. That's pretty much the end goal. If I can get more EPSPs, you can already imagine, if I had enough EPSPs to stagger on top of one another, I would eventually be able to hit that threshold potential. Well, how do I get these EPSPs to just summate or add on top of one another? I'm so glad you asked. There's a type of thing called summation or wave summation. That's what I want to talk about now. So let's come down here and take a look here. We're going to talk about two types of summations that we can get this type of like little add-ons of EPSPs to get that threshold potential because that's our goal. We want this. How do we get that? Well, the first one here is called temporal summation. Temporal summation. And temporal summation is like a like a gnat at a barbecue just bugging the stink out of you, right? It's just that just constantly just bugging at you. That's what this is. Here's our postsynaptic neuron, this neuron here. Here's our presynaptic neuron. And let's say that this is going to be releasing glutamate, right? So this is a stimulatory one. We'll put that stimulatory signal here. It can fire once, right? If it fires once, again, what's here? Resting membrane potential. What's our goal? Threshold potential. This is where we want to get to. This is negative 70. This is negative 55. Let's say this. Presynaptic neuron fires and triggers a EPSP. Gets there, doesn't reach threshold. Then fires again. It's a gnat, just bugging you. Adds on top of that one. Doesn't get there. Sends another stimulus. Adds on top of that one and boom. We hit our threshold voltage. Once you hit that threshold voltage, you can trigger the action potential. So that is the goal here. is that temporal summation is it's one presynaptic, presynaptic, spelled that wrong, presynaptic neuron repeatedly stimulating one postsynaptic neuron. And then whenever it's repeatedly stimulating that postsynaptic neuron, it's going to add on top of that. So again, Let's say here's one stimulus, two stimulus, three stimulus, that gets me to my threshold potential. That's how this works, this temporal summation. What's the other type of summation? Another way that we can get that resting membrane potential to threshold potential. It's called spatial summation. Spatial summation. Now spatial summation is kind of a similar concept. But now, instead of one neuron just bugging the stink out of you, you're going to have... three neurons firing simultaneously. So you have three presynaptic neurons. It's going to fire, it's going to fire, and it's going to fire all simultaneously. Oh, if that's the case, then if I all, and I have all of these, here's my resting membrane potential at negative 70 millivolts. Here's my threshold potential at negative 55 millivolts. If I have all three of these adding on to one another and summating, holy crap, I'm going to hit that threshold potential. That's how this works. So whenever you have two ways, right? One is temporal, one presynaptic, just on one postsynaptic neuron. Or spatial summation, which is multiple presynaptic neurons firing simultaneously on one postsynaptic neuron. And eventually, these EPSPs can summate. So these are the ways that we can get the resting membrane potential at negative 70 to Threshold potential, which is negative 55. And the way you can do it is by having more EPSPs than IPSPs. How do you get this many EPSPs? One is you just fire constantly from one neuron to the other, or multiple neurons firing simultaneously on one neuron. And you can add those EPSPs together to get you from resting membrane to threshold potential. Boom, on to action potential. Alright Ninja Nerds, so we're almost at the end of our story. We're at action potential. We went resting membrane, graded potentials, now we're at action potentials. Alright, so how did we get to this point here, right? So we started off at resting membrane potential, which was at what? Negative 70 millivolts, we said. We got ourselves to the actual threshold potential. What was our threshold potential? Our threshold potential was negative 55 millivolts. How did we get from the resting to threshold? We did it by the process of the graded potentials, the EPSPs, right? More of those than IPSPs, or summating them. Now, the reason why we've stressed so much about this voltage of negative 55 is that these purple channels, they're so sensitive to voltage, particularly that voltage. Let me kind of show you another diagram of what we're looking at here, before we start digging into this. We're taking a look at a neuron, right? Here's the cell body, here's the axon, and then here's going to be the terminal. Right now we've kind of focused primarily on what? We talked about the presynaptic neurons with the EPSPs and IPSPs. We took a look at the resting membrane potential. Well now what we're doing is we're looking at right here at this point. This is the axon hillock. Then all of this down here is our axon. And then this last point here which we're going to talk about is the axon terminal. So this is the final point of our actual journey here. within the neuron. Okay, this point here is actually of significant anatomical importance. You see how kind of the cell body narrows out towards the axon? There's a particular name for that. I like to call it the trigger zone, but textbooks love to call this the axon hillock. The axon hillock is your trigger zone. The trigger zone meaning that once you've hit a particular voltage inside of the cell, You can trigger an action potential by opening up these voltage-gated sodium channels that are highly concentrated at this area. Alright, so here we have it, this voltage-gated sodium channel. This voltage-gated sodium channel is normally closed, and we'll talk about how it closes. There's different types of gates. We'll get to that afterwards when we finish up with this last little graphical representation. For right now, just listen, and then whenever we go over it, it'll make sense. Once you hit a particular voltage, negative 55 millivolts, what that does is that activates these voltage-gated sodium channels, particularly what's called the activation gates on the outside. And once these activation gates are open, sodium ions will start rushing in very, very powerfully. Now, when the sodium ions move into the cell, they make the inside of the cell super positive, super positive. For example, you were at negative 55 millivolts. Whenever the sodium rushes in, it takes the voltage from negative 55 millivolts to positive 30 millivolts. Holy crap, it really flips the script, doesn't it? So whenever sodium comes in, it really rushes in and runs into the cell until you get from negative 55 to positive 30. Why positive 30? The reason why is, once you get positive 30 millivolts, there's another gate called the inactivation gate of this voltage-gated sodium channel that closes. And then because of that, sodium can no longer enter beyond that voltage. So you can actually remember two voltages. Negative 55 opens the activation gate of the voltage-gated sodium channel. And positive 30 closes the inactivation gate of the voltage-gated sodium channel. And that's why these numbers are coming up. Okay. Now, once we've done that, guess what happens? These positive ions that are in this side of the cell here, guess what they're gonna do? They're gonna come over here and they're gonna create a particular voltage, getting it to threshold at this particular voltage gate of sodium channel. Once you hit this, it was at negative 55, right? It's gonna open up and sodium is gonna rush into the cell. As sodium rushes into the cell, it's gonna make the inside of the cell super positive. And it's gonna flip the voltage from what? Negative 55 to... Positive 30 millivolts. And again, these positive ions are going to start moving down the axon. You see how it's moving down the axon? These positive ions are going to bring the inside of the cell here. Right, negative 70 millivolts. Getting it closer to threshold. Negative 55. Activating the voltage gate of sodium channels. Sodium will rush into the cell. Make the inside of the cell super positive. And flip the script here and switch it from what? Voltage. Negative 55 to positive 30. millivolts. Now there's a really important thing that I want you to see here. There's a trend. You see how we started at the axon hillock. We hit that particular voltage. We opened up the voltage gate of sodium channels. The sodium rushed in. When it rushed in, it flipped the inside of the cell, made it positive. But what's the next thing it did? Not only did it make the inside of the cell positive or another term, whenever you make the cell inside of the cell positive, is depolarized it. Where is that depolarizing or positive wave moving? down the axon. That's important. So this is called the action potential, which is the depolarizing wave or positively charged wave that's moving down the axon towards the terminal bulb. Now, here's where we got to go to the next part. These voltage-gated sodium channels, they actually will do what? They'll make the inside of the cell positive, right? Whenever they flush in. You know, there's another channel here, another special channel. This actually only activates whenever you hit positive 30 millivolts. So this is called a voltage-gated calcium channel. So this is called your calcium channel. It's a voltage-gated one. Only activated when you hit positive 30 millivolts. So sodium will rush in, makes the inside of the cell positive, around positive 30, opens up these voltage-gated calcium channels, and calcium will rush in to this axon terminal. When calcium rushes into the axon terminal, there's a specific reason for it. You know there's particular proteins, snare proteins, that are present on these vesicles and then present on the cell membrane of this axon terminal, right? Different types of snare proteins. What calcium does is it links these two proteins together. And when it links these two proteins together, guess what happens? They fuse. The synaptic vesicle fuses with the cell membrane. And when that synaptic vesicle fuses with the cell membrane, what does that look like? Whoop, whoop. And then what happens? All of these neurotransmitters or neuropeptides that are sitting inside of that actual vesicle are released out into this synaptic space. And what will they do? Well, maybe there's another cell. And then what happens is this neurotransmitter goes and binds onto this particular receptor. Okay, and if this neurotransmitter binds onto this particular receptor, it can exert its effects on this other cell, right? So I want you to see how we started off with resting membrane potential, got to the threshold, generated an action potential. Action potential moves down the axon, depolarizing wave. Depolarizing wave also moves over the axon terminal, opens up the voltage gate of calcium channels, calcium floods in. What's the purpose of that overarching theme? is calcium causes the fusion of the vesicles with the cell membrane and then the exocytosis of the neurotransmitters. Now we've stimulated this cell to like a son of a gun. Now what we got to do is we got to make the inside of the cell relax. We got to bring it, make it more negative again. Now there's terms that we got to get down, right? We use this term depolarize. I want to make sure we're completely clear on what that means. What does depolarize mean? It means you're making the cell positive. You're making the inside of the cell positive. That could mean that you started off negative, became positive, or you went from really negative to less negative. The whole point is that you're making the inside of the cell more positive than it previously was. The other term that we have to be aware of is called repolarization, right? So when you repolarize the cell, what is that? So you're repolarizing the cell, right? So basically, let's say that you started off at a positive voltage, right? You're taking that positive voltage and you're moving back to a negative voltage. But particularly that negative voltage you want to get to is resting membrane potential. That's really what repolarization is. The reason why I want to make it so clear that repolarization is going back to resting membrane potential, which is negative, is because there's another one we talked about, which is called hyperpolarization. And when you hyperpolarize your cell, you take a cell that is already negative. And make it even more negative. Okay? So those are the things I need you guys to understand. Depolarize, make it positive. Repolarize, you're going from positive back to negative. Arresting membrane potential. Hyperpolarize, you're making the cell even more negative than it already is. Alright, beautiful. Well, we've depolarized the heck out of this axon. And then axon terminal. Now we have to repolarize. Get it back to resting membrane potential. How do we do that? I'm glad you asked. See this positive 30 millivolts? This positive 30 millivolts may inactivate the inactivation gates of the sodium channels. But you know what they do? They activate these voltage-gated potassium channels. And then these voltage-gated potassium channels get what they allow for. They allow for the potassium to exit the cell. And when this potassium exits the cell, what happens to the inside of the cell? All these positive ions are leaking out of the cell. As that happens, it takes the voltage from where? Well, it was positive 30 millivolts, right? Potassium is going to leave and leave and leave out of the cell and takes it till it takes the voltage from positive 30 to negative 90 millivolts. To negative 90 millivolts. So it's really flipping the script here, right? So now the inside of the cell is going to be super negative. Okay, now same thing. Over here was positive 30 millivolts. So we were here at positive 30, stimulated the voltage-gated potassium. Potassium left, made this portion of the axon negative. Now we're back over here. This portion is positive, right? That voltage-gated sodium channel was activated. The sodium came in, made the inside of the cell positive, a positive 30 millivolts. That activated this voltage-gated potassium channel. After that voltage into potassium channel was stimulated, what happens? The potassium will leak out of the cell. And as these positive ions leak out of the cell, what does it do? It makes the inside of the cell negative. How negative? Well, it was positive 30 millivolts, takes it to negative 90 millivolts. Now, the next thing happens, right? Previously, we're kind of bifurcating so I can show you what happened. Previously, there was a positive 30 millivolts here that activated the voltage-gated calcium channels. They depolarized, calcium came in, triggered the neurotransmitter release. This calcium can't be in here just causing neurotransmitter to just be released all the time. We have to prevent this voltage-gated calcium channels from being open so that we can block the calcium from coming in and prevent any more neurotransmitter release. So let's pretend that that voltage-gated calcium channel was previously what voltage? Positive 30 millivolts, because that's where we were at before. Well, what happens is when you have this voltage-gated potassium channels open and potassium is leaving, that potassium, as it leaves, it's going to make the inside of the cell negative, right? And that's going to actually kind of bring the inside of the cell from what? Positive 30 millivolts to negative 90 millivolts. Guess what that negative 90 millivolts is going to do to that voltage-gated calcium channel? it's going to inhibit it. Once that voltage gated calcium channel is inhibited, calcium will no longer be able to enter into this cell. If calcium can't be brought into this cell, what's going to happen? Is it going to be able to bind here with these synaptic vesicles and fuse them with the cell membrane? No. Will neurotransmitter be released? No. So this is how all of this process happens. What I want you to understand is that this isn't happening like piece by piece by piece in the way that we talked about it. It actually happens like this. You hit threshold, you open up the voltage-gated sodium channels. They open, pop, pop, pop, pop, pop, all the way down. Okay? But as this is happening, as this depolarizing wave is moving down the axon, guess what's falling right behind it? The repolarization wave is also falling behind. to bring the inside of the cell back to resting membrane potential. Now, you'll notice something. You'll see here that I actually put it at negative 90 millivolts. Well, we said that resting membrane potential is negative 70 millivolts. It is. But what happens is, is potassium, when it leaves, these voltage-gated potassium channels, they're a little slow to close. So a little bit more potassium than usual is able to leak out and make the inside of the cell a little bit more negative and hyperpolarize it a little bit. But again, what three things contribute to bringing it back to resting membrane potential? Your sodium potassium ATPases, your leaky potassium channels, and your leaky sodium channels. So eventually, that negative 90 will go back to negative 70, and you'll get back to resting membrane potential. So, this is how an action potential occurs. Now, what we need to do is build on everything that we've talked about and talk about it in a graphical representation. Alright, engineers, so what we've got to do now is to put all of this stuff together. This is going to be a nice recap, but I actually have to add on one other thing that we said we were going to talk about, which is talking just a little bit more detail on those voltage-gated sodium channels, just to add on a little extra fact on that. Alright. So here we're going to have our graph, okay? Here on the x-axis, we got time. Here on the y-axis, we got voltage. Remember, what did we say was our resting membrane potential? Negative 70 millivolts about, right? That was our resting membrane potential, okay? We said our goal, what would actually, here, what got us to resting membrane potential? Sodium potassium ATPases, leaky potassium channels, leaky sodium channels. Which one was more permeable, potassium or sodium? Potassium. Now, the next thing we said we had to do is get from resting membrane potential to threshold potential. That was our next goal. And the threshold potential we said was around negative 55 millivolts. What got us from resting membrane potential to threshold potential? Our EPSPs, right? How did we get enough EPSPs to get us to threshold potential? Summation. What two ways? Temporal or spatial summation or just general wave summation, right? What were the waves? What were the types of... potentials that we're trying to inhibit and take it away from resting membrane your IPSPs they were trying to hyperpolarize it but if we're trying to stimulate let's say we start here at resting membrane we have an EPSP we summate we summate we summate we hit threshold potential once you hit threshold potential what voltage gated channels open up in the axon hillock the voltage gated sodium channels once those voltage gated sodium channels open The sodium will move into the cell until it hits about what voltage? About positive 30 millivolts, right? We said we were going to talk about what these voltage-gated sodium channels look like. Now it's important to know what they look like at resting membrane potential, at the peak of depolarization, and then what they look like as they're trying to go back towards resting membrane potential. All right, so let's say we start here at resting membrane potential. So at this point, what would those voltage-gated sodium channels look like? Well, if you took a look at one here, it would look something like this. Here's your channel. It has two gates. One gate is on the outside of the cell. So let's pretend here's our cell membrane here. Okay. It has a gate on the outside of the cell. And this gate is generally going to be closed at rest. This is called your activation gate. Then it has another gate on the inside of the cell. And this gate is usually open whenever the cell is. at rest. That's called your inactivation gate. Okay, so this is what it's going to look like at rest. Now, what happens is once you hit threshold potential, so once you hit this threshold potential, guess what happens to those voltage-gated sodium channels? The activation gates become activated, and the inactivation gates are also going to start being inhibited and start slowly closing. So what will that look like? As you hit threshold potential and you start moving up this rising phase of the action potential, those voltage-gated sodium channels will look like this. Okay, so now you're going to have here's your sodium channel and then again your activation gates are going to be opening like this and your inactivation gates are going to slowly be closing. So this is your inactivation gate and this is your activation gate and this is whenever it is stimulated. Okay, so it's hit threshold potential and it's undergoing the depolarization phase. This is what it would look like. And again, to give you an idea here, here's your cell membrane. Outside of the cells where the activation gate is, inside of the cells where the inactivation gate is. So this is what it would look like whenever the cell is, whenever this voltage gate of sodium channel is stimulated. You've hit threshold and you're moving up towards the rising phase of the action potential. Now, remember what I told you. Once we hit a particular voltage, positive 30 millivolts, what do we say happens? We said those voltage-gated sodium channels become inactivated. Really, it's the inactivation gate that finally closes. So now, if we go to the peak point, so this was like right here. This is the view that we got here, right? Once we hit threshold. Once we hit the peak point of the action potential, then what do we get? So here's our voltage-gated sodium channel. Now what happens is the inactivation gate is fully closed. and the activation gate is fully open and again To give you orientation here, here's going to be your cell membrane. Now this might look positive, right? Like in this situation here, ions can move in via the activation gate, right? And then again, ions cannot move in here. Look at this situation. You would think these positive ions could move in, but guess what's blocking them from getting into the cell? The inactivation gates. So the inactivation gates will not allow, because they're closed. They won't allow any more positive ions to come into the cell. So this is the configuration of the voltage-gated sodium channel when it is at positive 30 millivolts. So this is what it looks like at negative 55, and as you approach positive 30 millivolts. And this is what it looks like at negative 70 millivolts. Okay, we're at rest. Now, once we hit the positive 30 millivolts, these voltage-gated sodium channels become inactivated. What do we say? does activate at that point in time, the voltage-gated potassium channel is open. When the voltage-gated potassium channel is open, what do they do? Potassium starts leaking out of the cell. Now the cell is going to go from positive 32, negative 90 millivolts. It's going to repolarize as it approaches resting membrane potential. But what do we say? It hyperpolarizes a little bit. It becomes even more negative. How and why? It's because those voltage-gated potassium channels are a little bit slower to close. And so because of that... they just dip down a little bit lower, maybe negative 90 millivolts they dip. But then eventually via the sodium potassium ATPases, the leaky sodium channels, leaky potassium channels, eventually you'll get yourself back to resting membrane potential. Now, this is the configuration that I want you to remember, right? For the rest, what it looks like at rest, what it looks like when it's stimulated until it gets to the peak potential. But this is what it's going to be stuck in until you get where? Back to resting membrane potential. So until this voltage-gated sodium channel gets back to resting membrane potential, it's going to be stuck like that. But eventually, once it hits resting membrane potential, it'll go back into this configuration where the activation gate will close and the inactivation gate will open and it'll be ready to be stimulated again. In this situation, you can't stimulate this channel anymore. Because it's already at the peak voltage and there's just no way you're going to get those inactivation gates to open. All right? So because of that, this point, right? This point at which we kind of say from here, if I were to kind of mark a dotted line. This point here until we hit resting membrane potential. This point here from the peak point of the action potential until you hit the resting membrane potential. It doesn't matter what you do. You could stimulate this thing with the maximum voltage possible. Those inactivation gates are not going to become activated, and you're not going to be able to re-stimulate this cell. It has to get back into this configuration to be stimulated. So this period from here to here, there's a particular name for it that you have to know. This is called the absolute refractory period. It's called the absolute refractory period. What is this called? Absolute. refractory period. Can't stimulate it, doesn't matter how hard you try. But if you think about the next refractory period, there's another one. You have this cell going back into rest. Once it hits resting membrane potential, what does it go back into? What does these inactivation gates do? They open up, activation gates closes, and this is the configuration that it's able to be stimulated again. But look at where it is now. What do we say this voltage could be around? This might be somewhere around negative 90 millivolts, around that, right? Negative 90 millivolts is the voltage you're at. Threshold potential is negative 55. Generally, the only amount of energy you have to put into this cell is to go from negative 70 to negative 55. Now, if I wanted to stimulate this cell before it got back to resting membrane potential, just as it dipped under, I would have to go 20 extra voltage And then the additional voltage that I would have to get to from resting to threshold. So now I would have to go from here all the way to here. That's a lot more voltage. That's a lot more excessive stimulation I would have to give to this cell to excite it again and open up these voltage gated sodium channels. So the time period from when you hyperpolarize the cell until it goes back to resting membrane potential, there's another name for this. This is called the relative refractory Period. And this is the period where you can give a stimulus and you would be able to activate those voltage-gated sodium channels. But you have to add more voltage, more stimulus to get this from negative 90 to resting, and then from resting back to threshold potential. That's a lot of stimulus, but it is possible. It is not possible, however, with the absolute refractory. All right, Ninja Nerds, that covers everything that you'll need to know. about action potentials and all these other things we talked about. All right, Ningeners, in this video, we talk about resting membrane potentials, graded potentials, and action potentials. I hope you guys like this video, and I hope it helped. All right, Ningeners, you guys know what to do. As always, until next time. Thank you.

Go check that out. All right, let's go ahead and get started. All right, Ninjner, so what we have to do when we're talking about all of these membrane potentials within a neuron is we have to zoom in on the neuron, really talk about all that cellular processing and ion movement that is occurring here.

So first thing we have to talk about, since we're talking about all these potentials of a neuron, we have to start with resting membrane potential. Now, first thing we have to do is come up with just a basic definition of resting membrane potential. So how would you describe resting membrane potential? What is it?

Well, resting membrane potential is the voltage difference across this cell membrane when the cell is at rest. That's all it is. So it's the voltage difference across the cell, cell membrane.

At rest. And the next thing that you have to remember is, is yes, we're talking about this resting membrane potential existing in neurons, but resting membrane potentials can exist in every single cell. So it exists in all cells. That's very important to remember. We're just referring to it in this case in the neurons.

Okay. The next thing that you have to know is what is this actual wall. voltage, if we could put a value, a number on this voltage difference across the cell membrane at rest in a neuron, what would it be?

And it's actually a range. So I'm going to abbreviate resting membrane potential. Generally, this is a range. Now, most textbooks like Marriott says it's around negative 70 millivolts. That's kind of like the average.

Other textbooks will give it a little bit farther from that. The best way to kind of just cover all grounds is to say, generally, it could be somewhere between negative 70 millivolts to negative 90 millivolts with most textbooks supporting negative 70 millivolts is that kind of average number okay so that's kind of what we know about resting membrane potentials now what we need to do is I want you to understand what we're looking at because we're zooming in on a neuron so what I'm actually doing here is I'm taking a neuron right we're looking at a neuron like this all right here is going to be your axon your cell body And then here we're going to have the axon terminal. Okay. What I'm doing is I'm zooming in on this portion of the cell membrane and we're looking at that.

Okay. That's what we're doing here. So we're really zooming in on the cell membrane of this neuron and looking at the activity. So you have to have one question here. How in the heck does your resting membrane potential get to negative 70 to negative 90 millivolts?

How do we get it there? There's three ways that we get it there. One of the ways that we get it to that voltage, that negative 70 to negative 90, is sodium potassium ATPases. These sodium potassium ATPases, what they do is they're so interesting and they're so intelligent, and they pump three sodium ions out of the cell. So three cations or positive ions out of the cell.

And then they pump two potassium ions or two cations into the cell. Now, take a look at this. Let's pretend for a second we're starting at a particular voltage.

Let's say we're starting at zero millivolts. That's our imaginary start point of how we're going to get to negative 70 millivolts. So we're starting at zero millivolts.

Now when these sodium potassium ATPases are working, they're pumping three positive ions out and only bringing two positive ions in. Because of that, that makes the inside of the cell just a little bit more negative. Not significant, just a teensy bit negative.

Maybe it only takes it from 0 millivolts to negative 5 millivolts. So not a big change, but that's obviously due to the sodium potassium ATPases. So these are going to be one of the reasons, okay?

So what are these called here? These are called your sodium potassium ATPases. Now, that's one function.

One of the functions of the sodium potassium ATPases is... is to help to make the inside of the cell just slightly negative. The second reason that these are so important is that they establish the concentration gradient for sodium and potassium.

Now, what is it doing to the sodium, these pumps? It's pushing sodium out. So what is that doing? That's increasing the concentration of sodium outside the cell. And by contrast, the sodium concentration inside of the cell will be lower.

Okay? Now, It's also concentrating potassium into the cells, pushing lots of potassium in. So what that's going to do is that's going to increase the potassium concentration inside the cell. And in contrast, there'll be less potassium outside the cell. So there's two functions of these sodium potassium ATPases.

One is they generate a small negative charge inside of the cell at rest. The second reason, the second thing that they do is they generate concentration gradient for these ions to move. And that's going to be important for the next two things. that contribute to the resting membrane potential. Okay beautiful.

Now the second thing that contributes to the resting membrane potential are over here, these blue channels. Okay and that leads us to our next discussion. There's going to be lots of different channels within a neuron that contributes to all these different potentials, resting, graded, action.

When we're talking about resting membrane potential, these blue channels here are very special types of channels. They are called leaky potassium channels and what that means is is that there are these little proteins embedded in the cell membrane and they're always open and they allow for ions like potassium in this case to move in and out of the cell freely and keyword here passively okay now these potassium channels are super leaky so that's gonna allow for ions like potassium to move which direction would the potassium want to move Well remember, what did we just say over here with the concentration gradients? Potassium is higher inside of the cell because of these sodium potassium ATPases. So if potassium is higher outside the cell and it's lower outside the cell, where is it going to want to go? It's going to want to leave this cell and exit.

So all this potassium is going to start leaving the cell. So let's have this showing here that the potassium is leaving the cell and how is it leaving? It's leaving moving what? down its concentration gradient from high concentration to low concentration.

From the intracellular fluid to the extracellular fluid. Okay, beautiful. Now, as these positive ions, these potassium ions are leaving, what's happening to the inside of the cell?

Great question, guys. Potassium is actually bound normally inside of the cell. Potassium is bound to an anion. You see this?

I'm going to represent it as A. Okay, A is just your non-specific anion, negatively charged ion. What are these anions and why am I mentioning it?

These anions can be of two types, okay? These anions that I'm representing here as A-can be of two things. One is they can be phosphates.

You know phosphates are just really negatively charged ions, very difficult for them to move outside of the cell because of that charge. The other thing, oh, let me get my marker here. The other thing here is going to be proteins. Proteins. You know proteins are made up of amino acids, right?

Tons of amino acids. And these amino acids have lots of negative charges on them. Well, that's another reason they can't exit the cell.

But what did I say was the common thing with these? This has negative charges. This has negative charges. That's what makes it an ion. They love to interact with potassium, which is a cation.

So whenever potassium leaves, you would think, oh, the anion's also going to leave. No, it's too big and too charged to leave the cell. So because of that, whenever potassium leaves, it leaves behind an unoccupied anion. And now every time the potassium leaves, it leaves behind an unoccupied anion and makes the inside of the cell more and more and more negative. So now this is super negative inside of the cell.

What? voltage you're not going to believe this but if potassium could it would move outside of the cell until you got that voltage somewhere around let's say negative 90 millivolts let's say that it took the inside of the cell and flipped it from negative five went all the way down to negative 90 millivolts that was because of these leaky potassium channels now the last one that contributes so we have the sodium potassium pumps The leaky potassium channels, the last one that is going to contribute here to this resting membrane potential is your leaky sodium channels. Now, remember, there is other ions that can move in and out of these cells, calcium, chloride. I'm only considering sodium and potassium to be the main ions because those are the ones that are the most significant in this case. But do realize I could consider calcium and chloride as well.

But for right now, what I want you to remember is one is sodium potassium ATPases, second is leaky potassium channels, the third one here... is going to be the leaky sodium channels. Now these are leaky again they allow for sodium to move in or out of the cell. But again where is the concentration gradient of sodium? We already said it's higher outside the cell.

So if the concentration of sodium is higher outside the cell, in contrast it's lower inside the cell. So where will the sodium want to move? The sodium will then want to move into the cell down its concentration gradient.

As sodium moves into the cell, down its concentration gradient, it makes the inside of the cell positive. But here is the big thing, I can't stress this enough. This cell, in this case a neuron, is so many more times permeable to potassium than it is to sodium.

It'll allow for tons and tons of potassium to leak out of the cell, but only allow a little bit of sodium to come into the cell. So because of that, we have to, let's actually write this down. That potassium, when we talk about permeability, we'll kind of put like a little heading here, permeability factors, right?

When we're talking about that with the cell, potassium is significantly more permeable. This cell's way more permeable to potassium than it is to sodium. So potassium will make a big change, like go from negative five to negative 90, but the sodium, not much of it moves in.

So because of that, it might not make as significant as a change. Maybe it only takes it from negative 90 to negative 70 millivolts. And we've reached our resting membrane potential.

So to recap, what are the three components that are actually helping us with this? Sodium potassium ATPases, the leaky potassium channels, the leaky sodium channels. And if you really wanted to add other ones in, leaky calcium and leaky chloride channels.

But the same concept applies. Last thing that we have to talk about this because this does come up on your exams a lot is learning how to calculate what's called the Nernst potential for sodium, potassium, calcium, chloride. We're literally just going to go through the equation quickly.

All right. So when we talk about Nernst potential, really, I only want you to know the equation. And then really it's a plug and chug thing from here.

There really isn't much to this. It's more important for you to know when you use the Nernst potential and what that Nernst potential like formula is. Okay, so NERF potential.

The first thing that you need to know is when do you use it? So when do you use it? And that's a very important question.

Let's take for example potassium in this case. Okay, potassium we know is moving out of the cell down its concentration gradient. But as it moves outside of the cell, the inside of the cell becomes positive.

I'm sorry, becomes more negative, right? That negative charge inside the cell wants to pull some of the potassium back into the cell. That's called the electrostatic gradient. So potassium moves out of the cell down its concentration gradient, but kind of gets pulled back into the cell down its electrostatic gradient.

The point in time in which potassium is moving equally, or there's kind of like no net movement of potassium moving out of the cell down its concentration gradient, or moving into the cell down its electrostatic gradient, whenever those two are equal, that movement, you've reached NERTS potential. So we kind of write it like this. Whenever the potassium is moving out of the cell equals the potassium moving into the cell. And moving out is via its concentration gradient, right?

Its concentration gradient. And moving into the cell is via its electrostatic gradient. Then we can use the equation.

Well, then the next question is what is the equation? That equation is like this. We're going to write it for potassium. E for voltage. Okay, the equilibrium or the voltage that potassium is able to generate across that cell membrane at rest is equal to 61.5, which is a constant divided by Z, which is just basically the charge of the ion.

In this case, what's the charge of potassium? Plus one. What's 61.5 divided by plus one? 61.5. So we can just get rid of that.

Multiply by... log base 10, the concentration of potassium ions outside of the cell. And again, this is a value that you would get from a table or a textbook. And we're going to put down here five is the potassium concentration outside the cell. So this is here, right?

Another thing over here, there's the potassium concentration outside of the cell over the potassium concentration inside the cell. And again, this could be 150, right? If you calculate all of this out, That'll come somewhere around negative 90 millivolts. So that tells you that potassium will move outside of the cell until it'll move outside of the cell down its concentration gradient until the inside of the cell becomes negative 90 millivolts.

And then that movement down its electrostatic gradient keeps it in that kind of equilibrium point. Now, the same concept goes for sodium. If I wanted to calculate for sodium, I'd say equilibrium potential of sodium is equal to 61.5 divided by Z. It's a plus 1, so I don't need to, times log base 10. And then again, I'd have to kind of pull this number from a table.

And generally, that's like 140 for the sodium concentration outside of the cell, and then about 10 for the sodium concentration inside the cell. And then again, if you calculate all of this, you're going to get your equilibrium potential of sodium is somewhere around positive 70 millivolts. Now, if you added both of these up, negative 90 and positive 70, you're basically saying that your resting membrane potential is the equilibrium potential of potassium and the equilibrium potential of sodium. And if you did that, what would you get? Positive, you get negative 20 millivolts, negative 90 plus 70. But remember, what did I say?

It's a permeability thing. So potassium, there's going to be so much more potassium moving out of the cell. So the cell voltage will actually be closer to this equilibrium potential of potassium. So whenever you actually calculate this out, if you were to take a percentage and say, well, let's say that this cell is 90% permeable to potassium and only 10% permeable to sodium.

If you calculated all of this out and then added them together, you would probably get somewhere approximately around negative 70 millivolts. And that is kind of how we really get down into the nitty gritty of how to calculate out these voltages. All right. Good enough.

Graded potentials. All right, guys. So we talked about resting membrane potentials. Okay.

Now what we have to do is take that resting membrane potential, negative 70 millivolts we said about, right? How we figured that out we already talked about. Now what we got to do is we got to get that negative 70 millivolts to a threshold voltage. We're getting closer towards an action potential.

We're building a story is what we're doing here. Okay. So now the purpose of graded potentials, the true underlying purpose, is to either take the resting membrane potential, right, and move it closer to threshold, right? So if you're trying to move it closer to threshold voltage, right, which is that voltage that we need to open up voltage-gated sodium channels in the axon, that threshold voltage is generally negative 55 millivolts, approximately.

If I want to get my negative 70 millivolts to negative 55 millivolts, I need a slight depolarization, right? But you know what else? Sometimes we don't want to stimulate an axon.

Sometimes we don't want to stimulate an action potential. So another aspect of graded potentials is not just depolarizing or bringing it to threshold, but sometimes we can take that resting membrane potential at negative 70 millivolts and actually take it away from threshold and maybe bring it even lower than resting membrane potential, right? And we could actually take this maybe down to negative 90 millivolts. This is called hyper polarizing okay you're hyper polarizing the cell you're making it even more negative there's particular names for these and that's what we really have to discuss whenever you take the resting membrane potential and you try to bring it to threshold you're trying to excite this cell this neuron and we give a term for this we call this an e p s p an excitatory post-synaptic potential But then if you have another neuron that you're actually trying to inhibit, taking it farther away from threshold. Now look how much farther away we are from threshold.

We're at negative 90. It's going to be so hard to stimulate this neuron. So because of that, if you're really trying to inhibit this neuron, this is going to be called an IPSP, an inhibitory postsynaptic potential. Now, to give you an idea of what we're zooming in on and really looking at here, let's say we take another neuron. Here's our neuron, okay?

And here, we're going to have another neuron. We're going to have one neuron over here acting on this guy, and then we'll have another neuron right here acting on this. What we're doing is, is we're zooming in right here and taking a look at this portion here. We're zooming in here on this cell membrane, and we're taking a look at how these neurons are influencing this postsynaptic neuron. So again terminology.

These are called presynaptic neurons because this space here is called your synapse. This right here is After the synapse, so this is called your post synaptic neuron. So you have pre synaptic post synaptic neurons We're zooming in on that synapse.

Okay, first thing that I want you to know We're gonna have to have something that excites the cell So what we're gonna do is we're gonna give a stimulatory signal here. We're gonna call this Neuron here this neuron that's gonna be trying this pre synaptic neuron is going to try to excite this cell this post synaptic neuron And the way it's gonna do it is it's gonna release a particular neurotransmitter Let's just pick, in this case, a stimulatory neurotransmitter like glutamate. You know, glutamate is a very good stimulator within the central nervous system.

So what we're going to do is we're going to have glutamate bind onto this little receptor site. See how there's this little pocket there? That little pocket is important because once glutamate binds into it, normally what's happening is these channels are closed.

And we have to talk about what type of channel this is. Normally there's like a little gate there blocking it, right? There's a little gate there blocking any ions from coming in.

But once glutamate binds onto this little pocket, it lifts this gate up. And now what was closed over that kind of like porous surface is now opened up. Now look at the gate. It's popped up.

And now what happens is this opens up the channel for ions to flow in. What kind of ions? Any type of cation generally. Maybe it's sodium that'll flow into this cell. Maybe it's calcium that'll flow into this cell.

And as the sodium ions and the calcium ions start to move inside of the cell, it makes the inside of the cell positive. Well, remember, what was the voltage previously inside of the cell? We were at negative 70 millivolts.

And now what's going to happen is that these positive ions moving into the cell are going to try to start moving the inside of the cell towards that positive range, more positive. Maybe negative 55 millivolts is what we want it to get to. Okay, that's what this EPSP means. It brings in positive ions into the cell. How does it do that?

By the neurotransmitter glutamate binding to this type of channel. What is this channel here called? Whenever a ligand or neurotransmitter or chemical binds onto this pocket of this channel and opens it up.

This is called, it goes by many names, but I like to refer to them as ligand gated ion. channel. Okay? Alright, beautiful.

So these are your ligand-gated ion channels. And they're going to be one of the things, in this case, a stimulatory neurotransmitter bringing positive ions in. This is going to lead to this EPSP we talked about.

And we'll represent this graphically in a second. On the other situation, we have to have the opposing action, the IPSPs. So now what we're going to do is we're going to have an inhibitory neurotransmitter here. And this inhibitory neurotransmitter is going to release a particular neurotransmitter that's commonly going to cause inhibition.

What's this kind? This could be something like GABA, gamma-aminobutric acid. Gamma-aminobutric acid or GABA is actually going to bind onto this little pocket. And again, let's pretend that this little pocket had this gate closed, okay? But whenever GABA binds on, it stimulates this type of channel, and then what it does is it opens up.

that little gate that was previously blocking the opening. And what this does is this allows for chloride ions to come into the cell. So now you have chloride ions coming into the cell. Or it can allow for potassium ions to leave the cell. Now if potassium ions leave the cell, what do they leave behind?

Remember, what does potassium normally bound to? An anion. And these anions are proteins and phosphates and they can't leave the cell.

So whenever potassium leaves, it leaves behind the... anion. And if you leave behind the anions, that makes the inside of the cell negative.

If you bring chloride ions, which are negatively charged ions inside of the cell, what's that going to do? Make the inside of the cell negative. What was the previous voltage inside of the cell at rest before we even had this GABA acting on this ligand gated ion channel?

It was negative 70 millivolts. What happened is, is you brought in all these negative ions. in the form of chloride or at potassium ions leave cations leaving that made the inside of the cell negative and it hyperpolarized it and took it from negative 70 to negative um 90 millivolts let's say okay so it made it even more negative that is called a ipsp now here's the thing This is a constant battle.

There's a constant battle between this neuron. You can have multiple stimulatory and inhibitory signals acting on this one neuron. Your goal obviously is to have more EPSPs than IPSPs. But if you were to look at this in a graphical representation, on the x-axis we got time, milliseconds, and on the y-axis we've got millivolts.

Let's say here is my resting membrane potential, right? What was that voltage we said? Negative 70 millivolts, right?

What's my threshold? My threshold is negative 55 millivolts. That's where I want to get to so I can open up those voltage-gated sodium channels in the axon, trigger and action potential.

So that's going to be this pink line. This is my threshold potential. How do we try to get there? EPSPs, right? This is what we want.

We want stimulatory signals. We don't want as many inhibitory signals. But in life, that's not how everything always works. So sometimes what may happen is maybe you have an EPSP, right?

And that EPSP is getting close to that threshold potential, but it's just not enough. If you don't hit the threshold potential, you don't get an action potential, right? It's kind of that all or none phenomenon. So maybe what happens is you get to this point and you try to trigger, right, this depolarization and it just doesn't get there. Okay.

And then maybe what happens is you get another EPSP that fires. And maybe you just get a little bit closer, but you still don't hit that threshold potential. At the same time, you could also be having what else? You could also be having these IPSPs firing.

They could also be trying to bring the voltage below, and then another one fires and brings it below. So it's a constant battle between these two. How could we ever get the EPSPs and IPSPs to get to this point where I can hit the threshold?

The whole goal... is I need to have more EPSPs, right, than IPSPs. That's pretty much the end goal. If I can get more EPSPs, you can already imagine, if I had enough EPSPs to stagger on top of one another, I would eventually be able to hit that threshold potential.

Well, how do I get these EPSPs to just summate or add on top of one another? I'm so glad you asked. There's a type of thing called summation or wave summation.

That's what I want to talk about now. So let's come down here and take a look here. We're going to talk about two types of summations that we can get this type of like little add-ons of EPSPs to get that threshold potential because that's our goal. We want this.

How do we get that? Well, the first one here is called temporal summation. Temporal summation.

And temporal summation is like a like a gnat at a barbecue just bugging the stink out of you, right? It's just that just constantly just bugging at you. That's what this is. Here's our postsynaptic neuron, this neuron here.

Here's our presynaptic neuron. And let's say that this is going to be releasing glutamate, right? So this is a stimulatory one. We'll put that stimulatory signal here.

It can fire once, right? If it fires once, again, what's here? Resting membrane potential. What's our goal?

Threshold potential. This is where we want to get to. This is negative 70. This is negative 55. Let's say this. Presynaptic neuron fires and triggers a EPSP. Gets there, doesn't reach threshold.

Then fires again. It's a gnat, just bugging you. Adds on top of that one. Doesn't get there. Sends another stimulus.

Adds on top of that one and boom. We hit our threshold voltage. Once you hit that threshold voltage, you can trigger the action potential.

So that is the goal here. is that temporal summation is it's one presynaptic, presynaptic, spelled that wrong, presynaptic neuron repeatedly stimulating one postsynaptic neuron. And then whenever it's repeatedly stimulating that postsynaptic neuron, it's going to add on top of that. So again, Let's say here's one stimulus, two stimulus, three stimulus, that gets me to my threshold potential.

That's how this works, this temporal summation. What's the other type of summation? Another way that we can get that resting membrane potential to threshold potential.

It's called spatial summation. Spatial summation. Now spatial summation is kind of a similar concept.

But now, instead of one neuron just bugging the stink out of you, you're going to have... three neurons firing simultaneously. So you have three presynaptic neurons. It's going to fire, it's going to fire, and it's going to fire all simultaneously. Oh, if that's the case, then if I all, and I have all of these, here's my resting membrane potential at negative 70 millivolts.

Here's my threshold potential at negative 55 millivolts. If I have all three of these adding on to one another and summating, holy crap, I'm going to hit that threshold potential. That's how this works.

So whenever you have two ways, right? One is temporal, one presynaptic, just on one postsynaptic neuron. Or spatial summation, which is multiple presynaptic neurons firing simultaneously on one postsynaptic neuron. And eventually, these EPSPs can summate. So these are the ways that we can get the resting membrane potential at negative 70 to Threshold potential, which is negative 55. And the way you can do it is by having more EPSPs than IPSPs.

How do you get this many EPSPs? One is you just fire constantly from one neuron to the other, or multiple neurons firing simultaneously on one neuron. And you can add those EPSPs together to get you from resting membrane to threshold potential. Boom, on to action potential. Alright Ninja Nerds, so we're almost at the end of our story.

We're at action potential. We went resting membrane, graded potentials, now we're at action potentials. Alright, so how did we get to this point here, right? So we started off at resting membrane potential, which was at what? Negative 70 millivolts, we said.

We got ourselves to the actual threshold potential. What was our threshold potential? Our threshold potential was negative 55 millivolts. How did we get from the resting to threshold?

We did it by the process of the graded potentials, the EPSPs, right? More of those than IPSPs, or summating them. Now, the reason why we've stressed so much about this voltage of negative 55 is that these purple channels, they're so sensitive to voltage, particularly that voltage. Let me kind of show you another diagram of what we're looking at here, before we start digging into this.

We're taking a look at a neuron, right? Here's the cell body, here's the axon, and then here's going to be the terminal. Right now we've kind of focused primarily on what? We talked about the presynaptic neurons with the EPSPs and IPSPs. We took a look at the resting membrane potential.

Well now what we're doing is we're looking at right here at this point. This is the axon hillock. Then all of this down here is our axon. And then this last point here which we're going to talk about is the axon terminal.

So this is the final point of our actual journey here. within the neuron. Okay, this point here is actually of significant anatomical importance.

You see how kind of the cell body narrows out towards the axon? There's a particular name for that. I like to call it the trigger zone, but textbooks love to call this the axon hillock.

The axon hillock is your trigger zone. The trigger zone meaning that once you've hit a particular voltage inside of the cell, You can trigger an action potential by opening up these voltage-gated sodium channels that are highly concentrated at this area. Alright, so here we have it, this voltage-gated sodium channel. This voltage-gated sodium channel is normally closed, and we'll talk about how it closes.

There's different types of gates. We'll get to that afterwards when we finish up with this last little graphical representation. For right now, just listen, and then whenever we go over it, it'll make sense. Once you hit a particular voltage, negative 55 millivolts, what that does is that activates these voltage-gated sodium channels, particularly what's called the activation gates on the outside. And once these activation gates are open, sodium ions will start rushing in very, very powerfully.

Now, when the sodium ions move into the cell, they make the inside of the cell super positive, super positive. For example, you were at negative 55 millivolts. Whenever the sodium rushes in, it takes the voltage from negative 55 millivolts to positive 30 millivolts. Holy crap, it really flips the script, doesn't it? So whenever sodium comes in, it really rushes in and runs into the cell until you get from negative 55 to positive 30. Why positive 30?

The reason why is, once you get positive 30 millivolts, there's another gate called the inactivation gate of this voltage-gated sodium channel that closes. And then because of that, sodium can no longer enter beyond that voltage. So you can actually remember two voltages.

Negative 55 opens the activation gate of the voltage-gated sodium channel. And positive 30 closes the inactivation gate of the voltage-gated sodium channel. And that's why these numbers are coming up.

Okay. Now, once we've done that, guess what happens? These positive ions that are in this side of the cell here, guess what they're gonna do? They're gonna come over here and they're gonna create a particular voltage, getting it to threshold at this particular voltage gate of sodium channel. Once you hit this, it was at negative 55, right?

It's gonna open up and sodium is gonna rush into the cell. As sodium rushes into the cell, it's gonna make the inside of the cell super positive. And it's gonna flip the voltage from what? Negative 55 to... Positive 30 millivolts.

And again, these positive ions are going to start moving down the axon. You see how it's moving down the axon? These positive ions are going to bring the inside of the cell here.

Right, negative 70 millivolts. Getting it closer to threshold. Negative 55. Activating the voltage gate of sodium channels.

Sodium will rush into the cell. Make the inside of the cell super positive. And flip the script here and switch it from what? Voltage. Negative 55 to positive 30. millivolts.

Now there's a really important thing that I want you to see here. There's a trend. You see how we started at the axon hillock.

We hit that particular voltage. We opened up the voltage gate of sodium channels. The sodium rushed in.

When it rushed in, it flipped the inside of the cell, made it positive. But what's the next thing it did? Not only did it make the inside of the cell positive or another term, whenever you make the cell inside of the cell positive, is depolarized it.

Where is that depolarizing or positive wave moving? down the axon. That's important. So this is called the action potential, which is the depolarizing wave or positively charged wave that's moving down the axon towards the terminal bulb. Now, here's where we got to go to the next part.

These voltage-gated sodium channels, they actually will do what? They'll make the inside of the cell positive, right? Whenever they flush in.

You know, there's another channel here, another special channel. This actually only activates whenever you hit positive 30 millivolts. So this is called a voltage-gated calcium channel. So this is called your calcium channel. It's a voltage-gated one.

Only activated when you hit positive 30 millivolts. So sodium will rush in, makes the inside of the cell positive, around positive 30, opens up these voltage-gated calcium channels, and calcium will rush in to this axon terminal. When calcium rushes into the axon terminal, there's a specific reason for it. You know there's particular proteins, snare proteins, that are present on these vesicles and then present on the cell membrane of this axon terminal, right?

Different types of snare proteins. What calcium does is it links these two proteins together. And when it links these two proteins together, guess what happens? They fuse.

The synaptic vesicle fuses with the cell membrane. And when that synaptic vesicle fuses with the cell membrane, what does that look like? Whoop, whoop. And then what happens? All of these neurotransmitters or neuropeptides that are sitting inside of that actual vesicle are released out into this synaptic space.

And what will they do? Well, maybe there's another cell. And then what happens is this neurotransmitter goes and binds onto this particular receptor. Okay, and if this neurotransmitter binds onto this particular receptor, it can exert its effects on this other cell, right? So I want you to see how we started off with resting membrane potential, got to the threshold, generated an action potential.

Action potential moves down the axon, depolarizing wave. Depolarizing wave also moves over the axon terminal, opens up the voltage gate of calcium channels, calcium floods in. What's the purpose of that overarching theme? is calcium causes the fusion of the vesicles with the cell membrane and then the exocytosis of the neurotransmitters. Now we've stimulated this cell to like a son of a gun.

Now what we got to do is we got to make the inside of the cell relax. We got to bring it, make it more negative again. Now there's terms that we got to get down, right?

We use this term depolarize. I want to make sure we're completely clear on what that means. What does depolarize mean?

It means you're making the cell positive. You're making the inside of the cell positive. That could mean that you started off negative, became positive, or you went from really negative to less negative.

The whole point is that you're making the inside of the cell more positive than it previously was. The other term that we have to be aware of is called repolarization, right? So when you repolarize the cell, what is that? So you're repolarizing the cell, right? So basically, let's say that you started off at a positive voltage, right?

You're taking that positive voltage and you're moving back to a negative voltage. But particularly that negative voltage you want to get to is resting membrane potential. That's really what repolarization is.

The reason why I want to make it so clear that repolarization is going back to resting membrane potential, which is negative, is because there's another one we talked about, which is called hyperpolarization. And when you hyperpolarize your cell, you take a cell that is already negative. And make it even more negative. Okay?

So those are the things I need you guys to understand. Depolarize, make it positive. Repolarize, you're going from positive back to negative.

Arresting membrane potential. Hyperpolarize, you're making the cell even more negative than it already is. Alright, beautiful. Well, we've depolarized the heck out of this axon.

And then axon terminal. Now we have to repolarize. Get it back to resting membrane potential. How do we do that? I'm glad you asked.

See this positive 30 millivolts? This positive 30 millivolts may inactivate the inactivation gates of the sodium channels. But you know what they do?

They activate these voltage-gated potassium channels. And then these voltage-gated potassium channels get what they allow for. They allow for the potassium to exit the cell.

And when this potassium exits the cell, what happens to the inside of the cell? All these positive ions are leaking out of the cell. As that happens, it takes the voltage from where?

Well, it was positive 30 millivolts, right? Potassium is going to leave and leave and leave out of the cell and takes it till it takes the voltage from positive 30 to negative 90 millivolts. To negative 90 millivolts. So it's really flipping the script here, right? So now the inside of the cell is going to be super negative.

Okay, now same thing. Over here was positive 30 millivolts. So we were here at positive 30, stimulated the voltage-gated potassium. Potassium left, made this portion of the axon negative. Now we're back over here.

This portion is positive, right? That voltage-gated sodium channel was activated. The sodium came in, made the inside of the cell positive, a positive 30 millivolts.

That activated this voltage-gated potassium channel. After that voltage into potassium channel was stimulated, what happens? The potassium will leak out of the cell. And as these positive ions leak out of the cell, what does it do? It makes the inside of the cell negative.

How negative? Well, it was positive 30 millivolts, takes it to negative 90 millivolts. Now, the next thing happens, right? Previously, we're kind of bifurcating so I can show you what happened.

Previously, there was a positive 30 millivolts here that activated the voltage-gated calcium channels. They depolarized, calcium came in, triggered the neurotransmitter release. This calcium can't be in here just causing neurotransmitter to just be released all the time.

We have to prevent this voltage-gated calcium channels from being open so that we can block the calcium from coming in and prevent any more neurotransmitter release. So let's pretend that that voltage-gated calcium channel was previously what voltage? Positive 30 millivolts, because that's where we were at before. Well, what happens is when you have this voltage-gated potassium channels open and potassium is leaving, that potassium, as it leaves, it's going to make the inside of the cell negative, right? And that's going to actually kind of bring the inside of the cell from what?

Positive 30 millivolts to negative 90 millivolts. Guess what that negative 90 millivolts is going to do to that voltage-gated calcium channel? it's going to inhibit it. Once that voltage gated calcium channel is inhibited, calcium will no longer be able to enter into this cell. If calcium can't be brought into this cell, what's going to happen?

Is it going to be able to bind here with these synaptic vesicles and fuse them with the cell membrane? No. Will neurotransmitter be released? No.

So this is how all of this process happens. What I want you to understand is that this isn't happening like piece by piece by piece in the way that we talked about it. It actually happens like this. You hit threshold, you open up the voltage-gated sodium channels.

They open, pop, pop, pop, pop, pop, all the way down. Okay? But as this is happening, as this depolarizing wave is moving down the axon, guess what's falling right behind it? The repolarization wave is also falling behind. to bring the inside of the cell back to resting membrane potential.

Now, you'll notice something. You'll see here that I actually put it at negative 90 millivolts. Well, we said that resting membrane potential is negative 70 millivolts. It is. But what happens is, is potassium, when it leaves, these voltage-gated potassium channels, they're a little slow to close.

So a little bit more potassium than usual is able to leak out and make the inside of the cell a little bit more negative and hyperpolarize it a little bit. But again, what three things contribute to bringing it back to resting membrane potential? Your sodium potassium ATPases, your leaky potassium channels, and your leaky sodium channels. So eventually, that negative 90 will go back to negative 70, and you'll get back to resting membrane potential.

So, this is how an action potential occurs. Now, what we need to do is build on everything that we've talked about and talk about it in a graphical representation. Alright, engineers, so what we've got to do now is to put all of this stuff together. This is going to be a nice recap, but I actually have to add on one other thing that we said we were going to talk about, which is talking just a little bit more detail on those voltage-gated sodium channels, just to add on a little extra fact on that. Alright.

So here we're going to have our graph, okay? Here on the x-axis, we got time. Here on the y-axis, we got voltage. Remember, what did we say was our resting membrane potential?

Negative 70 millivolts about, right? That was our resting membrane potential, okay? We said our goal, what would actually, here, what got us to resting membrane potential?

Sodium potassium ATPases, leaky potassium channels, leaky sodium channels. Which one was more permeable, potassium or sodium? Potassium. Now, the next thing we said we had to do is get from resting membrane potential to threshold potential.

That was our next goal. And the threshold potential we said was around negative 55 millivolts. What got us from resting membrane potential to threshold potential? Our EPSPs, right?

How did we get enough EPSPs to get us to threshold potential? Summation. What two ways?

Temporal or spatial summation or just general wave summation, right? What were the waves? What were the types of... potentials that we're trying to inhibit and take it away from resting membrane your IPSPs they were trying to hyperpolarize it but if we're trying to stimulate let's say we start here at resting membrane we have an EPSP we summate we summate we summate we hit threshold potential once you hit threshold potential what voltage gated channels open up in the axon hillock the voltage gated sodium channels once those voltage gated sodium channels open The sodium will move into the cell until it hits about what voltage? About positive 30 millivolts, right?

We said we were going to talk about what these voltage-gated sodium channels look like. Now it's important to know what they look like at resting membrane potential, at the peak of depolarization, and then what they look like as they're trying to go back towards resting membrane potential. All right, so let's say we start here at resting membrane potential. So at this point, what would those voltage-gated sodium channels look like? Well, if you took a look at one here, it would look something like this.

Here's your channel. It has two gates. One gate is on the outside of the cell. So let's pretend here's our cell membrane here.

Okay. It has a gate on the outside of the cell. And this gate is generally going to be closed at rest.

This is called your activation gate. Then it has another gate on the inside of the cell. And this gate is usually open whenever the cell is. at rest. That's called your inactivation gate.

Okay, so this is what it's going to look like at rest. Now, what happens is once you hit threshold potential, so once you hit this threshold potential, guess what happens to those voltage-gated sodium channels? The activation gates become activated, and the inactivation gates are also going to start being inhibited and start slowly closing.

So what will that look like? As you hit threshold potential and you start moving up this rising phase of the action potential, those voltage-gated sodium channels will look like this. Okay, so now you're going to have here's your sodium channel and then again your activation gates are going to be opening like this and your inactivation gates are going to slowly be closing. So this is your inactivation gate and this is your activation gate and this is whenever it is stimulated.

Okay, so it's hit threshold potential and it's undergoing the depolarization phase. This is what it would look like. And again, to give you an idea here, here's your cell membrane. Outside of the cells where the activation gate is, inside of the cells where the inactivation gate is.

So this is what it would look like whenever the cell is, whenever this voltage gate of sodium channel is stimulated. You've hit threshold and you're moving up towards the rising phase of the action potential. Now, remember what I told you. Once we hit a particular voltage, positive 30 millivolts, what do we say happens? We said those voltage-gated sodium channels become inactivated.

Really, it's the inactivation gate that finally closes. So now, if we go to the peak point, so this was like right here. This is the view that we got here, right?

Once we hit threshold. Once we hit the peak point of the action potential, then what do we get? So here's our voltage-gated sodium channel. Now what happens is the inactivation gate is fully closed.

and the activation gate is fully open and again To give you orientation here, here's going to be your cell membrane. Now this might look positive, right? Like in this situation here, ions can move in via the activation gate, right? And then again, ions cannot move in here. Look at this situation.

You would think these positive ions could move in, but guess what's blocking them from getting into the cell? The inactivation gates. So the inactivation gates will not allow, because they're closed.

They won't allow any more positive ions to come into the cell. So this is the configuration of the voltage-gated sodium channel when it is at positive 30 millivolts. So this is what it looks like at negative 55, and as you approach positive 30 millivolts. And this is what it looks like at negative 70 millivolts. Okay, we're at rest.

Now, once we hit the positive 30 millivolts, these voltage-gated sodium channels become inactivated. What do we say? does activate at that point in time, the voltage-gated potassium channel is open. When the voltage-gated potassium channel is open, what do they do? Potassium starts leaking out of the cell.

Now the cell is going to go from positive 32, negative 90 millivolts. It's going to repolarize as it approaches resting membrane potential. But what do we say? It hyperpolarizes a little bit.

It becomes even more negative. How and why? It's because those voltage-gated potassium channels are a little bit slower to close. And so because of that... they just dip down a little bit lower, maybe negative 90 millivolts they dip.

But then eventually via the sodium potassium ATPases, the leaky sodium channels, leaky potassium channels, eventually you'll get yourself back to resting membrane potential. Now, this is the configuration that I want you to remember, right? For the rest, what it looks like at rest, what it looks like when it's stimulated until it gets to the peak potential. But this is what it's going to be stuck in until you get where?

Back to resting membrane potential. So until this voltage-gated sodium channel gets back to resting membrane potential, it's going to be stuck like that. But eventually, once it hits resting membrane potential, it'll go back into this configuration where the activation gate will close and the inactivation gate will open and it'll be ready to be stimulated again.

In this situation, you can't stimulate this channel anymore. Because it's already at the peak voltage and there's just no way you're going to get those inactivation gates to open. All right?

So because of that, this point, right? This point at which we kind of say from here, if I were to kind of mark a dotted line. This point here until we hit resting membrane potential.

This point here from the peak point of the action potential until you hit the resting membrane potential. It doesn't matter what you do. You could stimulate this thing with the maximum voltage possible. Those inactivation gates are not going to become activated, and you're not going to be able to re-stimulate this cell.

It has to get back into this configuration to be stimulated. So this period from here to here, there's a particular name for it that you have to know. This is called the absolute refractory period.

It's called the absolute refractory period. What is this called? Absolute.

refractory period. Can't stimulate it, doesn't matter how hard you try. But if you think about the next refractory period, there's another one.

You have this cell going back into rest. Once it hits resting membrane potential, what does it go back into? What does these inactivation gates do?

They open up, activation gates closes, and this is the configuration that it's able to be stimulated again. But look at where it is now. What do we say this voltage could be around?

This might be somewhere around negative 90 millivolts, around that, right? Negative 90 millivolts is the voltage you're at. Threshold potential is negative 55. Generally, the only amount of energy you have to put into this cell is to go from negative 70 to negative 55. Now, if I wanted to stimulate this cell before it got back to resting membrane potential, just as it dipped under, I would have to go 20 extra voltage And then the additional voltage that I would have to get to from resting to threshold. So now I would have to go from here all the way to here. That's a lot more voltage.

That's a lot more excessive stimulation I would have to give to this cell to excite it again and open up these voltage gated sodium channels. So the time period from when you hyperpolarize the cell until it goes back to resting membrane potential, there's another name for this. This is called the relative refractory Period. And this is the period where you can give a stimulus and you would be able to activate those voltage-gated sodium channels.

But you have to add more voltage, more stimulus to get this from negative 90 to resting, and then from resting back to threshold potential. That's a lot of stimulus, but it is possible. It is not possible, however, with the absolute refractory.

All right, Ninja Nerds, that covers everything that you'll need to know. about action potentials and all these other things we talked about. All right, Ningeners, in this video, we talk about resting membrane potentials, graded potentials, and action potentials.

I hope you guys like this video, and I hope it helped. All right, Ningeners, you guys know what to do. As always, until next time.

Thank you.

Transcript for:Neuronal Membrane Potentials Explained

Transcript for:
Neuronal Membrane Potentials Explained