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 ninja nurse 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 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 potentially 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 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 a resting membrane potential generally this is a range now most textbooks like maria 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 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 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 atp aces 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 are 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 zero millivolts to negative five millivolts so not a big change but that's obviously due to the sodium potassium atp aces 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 atp aces 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 cell it's 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 that they're 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 key word here passively okay now these potassium channels are super leaky so that's going to 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 the sodium potassium to p aces 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 gene your nonspecific 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 minus can be of two things one is they can be phosphates and 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 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 is 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 with 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 chambers now remember there is other ions that can move in and out of these cells calcium chloride i'm only considering 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 that sells way more permeable to potassium than it is to sodium so potassium will make a big change like go from negative 5 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 nerd's 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 nurse potential and and what that nurse potential like formula is okay so nerd's 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 and so it 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 it's 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 nerd's 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 cells 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 5 is the potassium concentration outside the cell so this is here right another thing over here this is 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 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 uh equilibrium point now the same concept goes for sodium if i wanted to calculate for sodium i say equilibrium potential of sodium is equal to 61.5 divided by z it's a plus one 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 uh 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 in 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 percent 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 we got to do is we got to get that negative 70 millivolts to a threshold voltage we're getting closer towards an action position we're building a story is what we're doing here okay so now what 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 postsynaptic 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 postsynaptic neuron so you have presynaptic postsynaptic neurons we're zooming in on that synapse okay first thing that i want you to know we're going to have to have something that excites the cell so what we're going to do is we're going to give a stimulatory signal here we're going to call this neuron here this neuron that's going to be trying this pre-synaptic neuron is going to try to excite this cell this postsynaptic neuron and the way it's going to do it is it's going to 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 there's this little like a 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 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 that 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 all right beautiful so these are your ligand-gated ion channels and they're going to be one of the things in this case the 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 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-aminobutyric 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 then 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 hyper polarized it and took it from negative 70 to negative 90 millivolts let's say okay so it made it even more negative that is called a i 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 up open up those voltage-gated sodium channels in the axon trigger an 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 eps ps you can already imagine if i had enough eps piece to stagger on top of one another i would eventually be able to hit that threshold potential well how do i get these eps fees 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 epsp's 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 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 in 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 pre-synaptic pre-synaptic spell that wrong pre-synaptic 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 just bugging the stink out of you you're going gonna have three neurons firing simultaneously so you have three presynaptic neuron it's gonna fire it's gonna fire and it's gonna fire all simultaneously 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 gonna 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 pre-synaptic 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 onto action potential all right ninja so we're almost at the end of our story we're at action potential we want resting membrane graded potentials now we're at action potentials all right so how do we how do 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 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 greater potentials the epsps right more of those than ipsb's 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 epsb's and ipsb's 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 all right so here we have it this voltage-gated sodium channel this voltage aided 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 this little graphical representation for right now just listen and then whenever we go over 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 this 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 have 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 you get a 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 going to do they're going to come over here and they're going to create a particular voltage getting it to threshold at this particular voltage gated sodium channel once you hit this it was at negative 55 right it's going to open up and sodium is going to rush into the cell as sodium rushes into the cell it's going to make the inside of the cell super positive and it's going to 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 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 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 well 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 this particular protein 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 at 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-gated 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 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 depolarized 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 that need you guys to understand depolarize make it positive repolarize you're going from positive back to negative or resting membrane potential hyperpolarizes you're making the cell even more negative than it already is all right 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 gets 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 gate of 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 heated 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 it takes it to negative 90 millivolts now the next thing happens right previously this 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 cause a 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's 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 too 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 being released no so this is how all of this process happens so what i want you to understand is that this isn't happening like piece by piece by piece and 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 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 following behind it 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 the resting membrane but bringing it back to resting memory 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 is build on everything that we've talked about and talk about it in a graphical representation all right engineer so what we're going to do now is to put all of this stuff together this is going to be a nice recap but i'm going to 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 all right 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 well 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 eps ps 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 were 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 sum it we sum eight 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 the cells where the inactivation gate is so this is what it would look like whenever the cell is whenever this voltage-gated 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 did we say happens we said those voltage-gated sodium channels become inactivated well 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 have threshold once we hit the peak point of the action potential then what do we get so here's our voltage gate to 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 or 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 gate of potassium channels open when the voltage-gated potassium channels 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 becomes even more negative how and why it's because those but 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 atp aces 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 wear 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 pair what's 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'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 the cells 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 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 the 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 that is 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 period all right ninja nerds that covers everything that you need to know about action potentials and all these other things we talked about all right ninjas 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 engineers you guys know what to do as always until next time [Music] you