Alright guys, so if you guys have already watched the video previously where we talk about the neuromuscular junction, specifically the neurotransmission, all the action potentials and the forming of acetylcholine and the releasing of acetylcholine, then you guys should be caught up to this point. Alright, so now what we're going to do in this video... we're going to talk about how acetylcholine is stimulating this muscle cell to develop what's called a end plate potential and then eventually an action potential. All right, so let's start here. Before we do that though, acetylcholine has to diffuse across this space.
Okay, this whole space. So if you imagine here, let's say I make a line from this point here all the way to this point here, right? So from this point here to this point here.
This space is called the synaptic cleft. Okay, so what happens is when acetylcholine is released by exocytosis, it moves across or diffuses. So it moves from high concentration to low concentration.
It diffuses across the synaptic cleft. diffuses across the synaptic cleft it comes to this postsynaptic membrane or this muscle cell membrane. When it gets to this muscle cell membrane you see how the muscle is kind of like folded in where the actual neuron is actually binding here and coming to that actual site to release the neurotransmitters. This folding here is called the post junctional folds. Let's write that down.
So again what is this folding here called? It's called the post junctional folds. And that allows for a nice surface area for this actual muscle cell to receive this stimulus from this actual motor neuron. Okay, so we have these post-junctional folds. We have the synaptic cleft.
We have acetylcholine moving and diffusing across the synaptic cleft to these actual muscle cell membrane. On the muscle cell membrane where these actual post-junctional folds are, you have these purple channels in large abundant amounts. These purple channels are actually what's called ligand gated ion channels. So again, what are these purple channels here called?
Or what type of channel I should say specifically. This channel is specifically called a ligand. Gated Ion Channel So this ligand gated ion channel is specific now. What is a ligand a ligand is a substance that's Binding on to this actual channel protein and facilitating some type of change What do you think the actual ligand is guys? It's acetylcholine Acetylcholine, when it diffuses across this synaptic cleft, it comes over here and it binds onto this actual pocket here.
This is a specific type of ligand-gated ion channel. This specific type of ligand-gated ion channel is called a nicotinic receptor. And what's really cool about this receptor is it's actually a pentameric protein. What does that mean to be pentameric? It means it has five proteins.
It's not super important that I mention, but I'm going to do it anyway, because that's what you get at Ningenert Science. You get extra. All right, so let's say here I have this protein here, and I have it looking like this channel. Here's the central hole where the ions are moving. There's five proteins that are involved in this.
So one, two, three. So one, two, three, four. One, two, three, four.
And then we got. got the five there. Okay.
There's an alpha, another alpha, a beta, a gamma, and a delta protein. So five protein subunits are making up this whole nicotinic receptor or nicotinic ligand gated ion channel. So it's a pentameric protein.
And again, they sometimes even write it like this. You might even see it sometimes written like this, A2 beta. And then you go.
So delta and then gamma protein. So sometimes they even write it like that. Alpha 2 beta delta gamma protein. And it's a nicotinic receptor, specifically type 1. If we really be specific, it's type 1. And it's a pentameric protein.
Now, when acetylcholine binds onto a specific receptor binding site or a specific domain on this pentameric protein, this nicotinic receptor, Normally when this cell is at rest, so let's say that this cell is at rest, what does that mean for a cell to be at rest? Now we have to talk about really quickly what's called resting membrane potential. So let's come over here to this graph and look at this graph for a second.
So inside of a cell, a cell has a point on this graph. So here, just real quickly on the graph, on time, on the x-axis, is where it's actually going to be in like our millisecond time. And here, on the y-axis, is going to be the voltage, which we're going to have in millivolts. Now, in every cell, they have what's called, almost every cell, they have what's called a resting membrane potential, which is a voltage that is actually going to be, more specifically, developed on the inside of the actual cell membrane as compared to the outside.
Generally, in skeletal muscle cells, their resting membrane potential is about negative 90 millivolts. A little bit more negative than neurons, which are negative 70 millivolts. Now, when this is at resting membrane potential, what's actually keeping this actual cell at resting membrane potential? So here at negative 90 millivolts, I'm going to write this here on the side.
This is the point of resting membrane potential. Now what I'm going to do briefly is I'm going to talk briefly about what's helping to maintain this resting membrane potential. Because for me to just talk about it and not even go over it, it's not going to help you guys.
I want to explain it a little bit more. So now, let me come over here to this side point over here. So what I'm going to do right here is I'm going to take a look at this actual side here.
On this actual muscle cell membrane, all across the muscle cell membrane, I'm just looking at this one point. There's special types of proteins. Special types of proteins. And these proteins are found in almost every single cell in our entire body. And they're special proteins, extremely important.
And what they're doing is, they're taking and pumping one thing out and pumping another thing in. So let's show that. Let's say that I pump this thing out, and I pump this thing in.
What I'm doing is... I'm pumping three sodium ions out of the cell. And I'm pumping two potassium ions into the cell. Now, I want you guys to think about this for a second. Just think logically.
Is there more positive ions going out than positive ions are coming in? There's more positive ions leaving than positive ions are coming in. So what does that mean?
What's the net result that's actually going to be happening here inside of this actual cell? It's going to develop a little bit more of an electro. positive charge. So because of that, I'm sorry, electro negative charge. So again, three sodium are moving out of the cell, two potassium are moving into the cell.
More positive ions are leaving than positive ions are coming in. So the cell is becoming more electro negative, but that's not enough. So this is helping to contribute to electro negative charge. But that's not enough, unfortunately. You know what else is really special?
We have other specialized channels. These passive leaky channels. We have these leaky channels inside of the actual cell membrane, and they're all across the cell membrane.
Don't get this purple protein confused with this protein. They're completely different. This channel is always usually open. And what happens is potassium ions are a much higher concentration inside the cell than they are outside the cell. So the potassium concentration, Outside the cell is much lower than the potassium concentration inside the cell.
Okay, it's usually a lot higher. So where do things like to move generally by the diffusion principle? They like to move from high to low concentration. And that's what potassium does.
Now think about this now. If more positive ions are leaving in contribution to this, what else is going to happen? You're going to develop even more electronegative charge.
And this is what's helping to maintain our resting membrane potential. Okay? So again, what are the two things that are maintaining the resting membrane potential?
One is the sodium-potassium pumps. Oh, sorry, we've got to come back down here for just a second. And the reason why is, what did I tell you? Potassium is in higher concentration where?
In the cell, lower concentration outside the cell. And the same thing is true for sodium. Sodium is in higher concentration. outside of the cell and it is in lower concentration inside the cell.
Where would it want to move? It would want to move this way, but we're pumping it against its concentration gradient. Therefore, when you pump things against their concentration gradient, what does that require?
That requires the use of ATP. So this is a primary act of transport. Just wanted to mention that really quick.
It's an important concept. So, generally, what is keeping our cell at resting membrane potential at approximately negative 90 millivolts? One thing is, specifically...
The sodium potassium ATPases. They're having more positive ions going out of the cell. than positive ions coming into the cell.
Second thing was those passive potassium leakage channels. Potassium is leaking out by its concentration gradient and causing the cell to become more electronegative. That's the resting membrane potential.
Now, what happens is acetylcholine starts moving across this synaptic cleft and binding onto, what are these channels here again? it starts binding onto these nicotinic receptors, right? So these nicotinic receptors type 1, which is a pentameric protein consisting of two alpha chains, a beta, a gamma, and a delta chain, right? When acetylcholine binds, these channels normally at rest are closed.
You see this point here? You see these little things here? They're blocking ions from being able to get in. So normally, because this channel is actually at rest, because this cell is at rest, these ions are getting repelled out. But then...
Because these positive ions are being repelled or whatever ions are being repelled because they can't be brought in. Because this gate, there's a gate blocking it from being able to come in. Because that's what it is, it's a ligand-gated ion channel.
Once acetylcholine binds onto this receptor domain, guess what happens to these channels here, these little gates? They open. And when that gate opens, what happens?
Ions can start flowing in and out. Because this is a bidirectional protein, it's not that specific. So what happens is... Sodium ions are generally in higher concentration outside of the cell.
So sodium is going to want to move down his concentration gradient from the actual outside of the cell or the extracellular matrix into the intracellular fluid, right? So sodium is going to move down his concentration gradient. But at the same time there's another ion who decides, you know what, I'm actually going to go out also.
And that is potassium. And potassium, his concentration gradient is the same. It's higher in here. and lower out here. So it's going to want to move from high to low concentrations.
Here's the thing though, what's really cool about this is this channel is so smart, it's so intelligent. And the reason why it's so intelligent is because it allows a little bit more sodium to come in and then potassium is going out. So less potassium is leaving, more sodium is coming in. What does that mean for the inside of the cell then?
Think about it logically again. Let's say five sodiums are coming in and two potassiums are going out. If I have more positive ions coming in than positive ions are going out, what is going to happen to the inside of the cell? It's going to have more positive ions, right? Because again, why is it going to have more positive ions?
Just to think about it logically. More sodium ions with a positive charge are coming in than these actual... Potassium ions with a positive charge are going out.
So it's becoming more electropositive. That's really interesting. So what would happen here at this one too? Same thing.
So just to repeat that whole process again, what would happen when acetylcholine binds? Normally this gate is blocking ions from coming in. When acetylcholine binds onto this receptor, it opens up this channel.
When it opens up the channel, what ions start flowing? In. Sodium ions flow in, down the concentration gradient.
Who's coming? Out. Potassium ions are flowing out, down their concentration gradient. But again, more sodium ions are flowing in than potassium ions are flowing out. And just to reiterate it one last time because now you guys will never forget, acetylcholine binds onto this receptor.
When it binds onto this receptor, it opens up these gates. When it opens up the gates, again, who flows in? Sodium ions. And if sodium ions start flowing in, and then there's another guy, Potassium. Potassium starts flowing out.
They go down their concentration gradients, but again more sodium is going out. I'm sorry, more sodium is coming in than potassium is going out. And again what will happen to this part here?
If more positive ions are coming in and less positive ions are going out, it'll become positive here. What about over here? It'll become positive over here too.
Look what happens. These are scattered throughout the entire higher membrane. I'm just zooming in on one point of these nicotinic receptors. If this is happening all across this membrane, what does it look like it's going to happen then? It's going to be like a nice wave, right?
That's kind of developing. A little positive charges that are developing. This is really, really important.
Now, what I'm going to do is I'm going to explain what's happening here on the graph again. So, due to those ligand-gated ion channels, they start changing the inside of the cell's potential. They start making it a little bit more positive.
So normally it was negative 90, which is really negative, right? But due to those sodium channels, I mean, so due to the sodium ions coming in more than potassium ions are going out. it starts rising a little bit. It starts becoming a little bit more electropositive. You know, every cell generally, mostly every, any excitable cell generally has a threshold potential.
So over here on the right, I'm going to write that down. I'm going to put TP, which stands for threshold potential. So threshold potential.
Every cell generally, every excitable cell has a threshold potential. What is the threshold potential generally in the skeletal muscle cell? It's a...
approximately about negative 55. So approximately about negative 55 millivolts. Now let's show this part in green representing the electropositive charge. So look what happens here it was originally a negative 90 right but due to the actual what was happening there with the actual acetylcholine and stuff like that causing the ions to come in it starts causing it to move Ports threshold potential.
What is that called? It's not an action potential. It's weird.
It's kind of like a graded potential. It's bringing it and having all this summation get up to that point. What is that called?
This right here, this specific event right here where these sodium ions more coming in, the potassium ions are going out, making the cell more electropositive is referred to as the end plate potential. Sometimes they even refer to it like a motor end plate potential. We're just going to call this an EPP or an end plate potential.
So what this end plate potential is doing is, is it's bringing the actual membrane voltage from negative 90 towards threshold. Why is that important? Okay, so let's mark this down here. So what is this event right here?
What's bringing this this way? This is the what? End plate potential. So the end plate potential is what's bringing the actual Membrane voltage from resting memory potential to threshold. Once that happens, you see this green protein right here?
Now this protein, this green protein has two gates. Okay, you see this little ball and chain like looking one? That ball and chain like looking one is called the inactivation gate. So this one's called the inactivation gate, okay?
Then if you look here, you can kind of see like this little green extension part of the protein on the bottom. You see that little green extension part there of the protein on the bottom? That right there is called the activation gate.
Okay? So let's, like, look at this. That right there is the inactivation gate.
And this part right here is called the activation gate. Why am I telling you this? Okay. You see all these positive charges that are accumulating because of that end plate potential? This activation gate will actually open.
So normally it's blocking ions from coming in. But when this activation gate is able to sense a specific voltage, in other words, threshold voltage. So what was threshold voltage? Negative 55 millivolts.
So let's say that this activation gate, it's stimulated, but by what voltage? Approximately negative 55 millivolts, which is our threshold. potential. What did we say would happen? If this activation gate is stimulated because of this in-plate potential, right, this in-plate potential is being developed, what happens to this activation gate?
It opens up. So now look, look at this. Now it's no longer blocking that entry. What can start happening now? What starts happening is a special ion starts flowing in really fast.
That ion is called sodium. Okay, let's do that with this nice blue color. Let's do, that's a nice color. So that's sodium coming in. Let me repeat this one more time.
The inside of the cell is becoming more positive due to the acetylcholine binding onto the ligand-gated ion channels or the nicotinic receptors, type 1. When they come in, more positive ions are coming in than positive ions are going out. Develops a end-plate potential. The cell becomes more positive, brings the actual cell membrane potential to function.
Threshold potential. When you reach threshold potential, the activation gate on this voltage sensitive sodium channel becomes activated when you reach threshold potential. Once that happens, the activation gate opens and sodium can flow in.
So again, what would happen to this activation gate? It would open. What would happen to this activation gate? It would open.
Once these bad boys open, what starts happening to these guys? Sodium starts flowing in. And it's not just a little bit of sodium. We're talking, you know, a beastly amount. A lot of sodium is coming in.
So if large amounts of sodium is rushing into the cell, what's happening? I'm going to represent this with a different color now. Look at this.
A whole bunch of positive charges are accumulating. of the cell and these positive charges are becoming very very important because what happens is as sodium rushes in through these voltage sensitive calcium sorry voltage sensitive sodium channels remember I'm only looking at this one point here. They are scattered all the way across this membrane. You know where else they're also present?
Right here. And we'll talk about this in just a second. We'll get there in a second. We'll come back to that.
But here, I want you guys to see something now. As this actual sodium starts coming in and coming in and coming in due to this actual movement from high concentration to low concentration through this actual voltage. What are these channels here called?
Let's write these channels down. What are these actual green channels? channels here, Cole.
These green channels are specifically voltage sensitive or gated, we can even put gated, voltage sensitive or gated sodium channels. And I want you guys to remember that they have an activation gate and an inactivation gate. The activation gate is stimulated when you reach threshold potential.
But, when you reach threshold potential and the activation gate opens, the sodium keeps flowing in and flowing in until the inside of the cell becomes extremely positive. Now let's show you what happens with that point. So I'm going to show this in blue representing the sodium flushing in.
Look what happens. It goes super, super, super, super, super high. And it reaches this peak point of electro voltage or the electrochemical voltage.
That peak point is approximately about positive 30 millivolts. So this is the peak point of the actual voltage inside of the cell. Why?
Okay. I told you about the activation gate. Now we have to talk about the inactivation gate.
So generally the inactivation gate just has that little ball just hanging over here, right? But what happens is once you reach the peak potential, what was that potential? the peak depolarizing potential approximately about positive 30 millivolts. So once you reach that depolarizing point, what happens to this actual inactivation gate?
Generally he wasn't blocking it. But then what happens is once it reaches this point here of positive 30 millivolts, the highest point of depolarization, look what happens to this sucker. He decides he's going to flip that big old ball in there.
And look what happens. He blocks this actual channel. And now sodium can't come rushing in. So again, one more time. Sodium was rushing in previously because the activation gate was open due to it reaching threshold potential.
But once you hit threshold, sodium can't come rushing in. starts flushing in and it flushes in until the actual membrane potential in the cell starts going up and up and up and up until it reaches positive 30 millivolts. Once it hits positive 30 millivolts the inactivation gates become stimulated and they start closing this actual sodium channel and then sodium can't come in.
Now, this point here is called the depolarizing current or the action potential. So this is depolarization and this is what's going to produce the action potential. An action potential is just basically whenever there's a flow of positive charges or due to the sodium ions moving across the actual cell membrane.
But here's what's really cool. You see how we follow this actual cell membrane? Again, what do we call the actual cell membrane? What do we call the plasma membrane of a muscle cell? That was important.
We should write that down. What was that called? What was this plasma cell membrane here called?
It was called the sarco... Lemma. And if you guys remember, what was the connective tissue covering right above the sarcolemma?
That was the endomycium, right? The areola connective tissue. Alright, now what happens is if you follow this sarcolemma, look what happens. It makes this little invagination.
There's a little invagination here of the sarcolemma. That invagination of the sarcolemma is a specific structure and they're scattered throughout the entire skeletal muscle cell. This right here is specifically called the transverse. Sometimes they just say T-tubule. So the transverse is the T, so the T stands for transverse.
So you can call it transverse tubule. or t-tubule. These t-tubules or transverse tubules are just invaginations of the sarcolemma.
Why is that important? Because this is sarcolemma, that must be sarcolemma also. Look what happens here. These positive charges that we developed, they start moving all the way along this membrane here.
What other channel would be right here in this area? Again, more voltage, you know, more voltage gated sodium channels. They're all the way across this thing.
So as this voltage gated sodium channels start opening up all the way across this actual sarcolemma, why is that significant? All right. Let's keep following this bad boy down.
Let's fix this part here. Make that nice. Okay.
Now. As the positive charges start moving down this T-tubule, you see this purple protein right there? It's a very special protein, very special protein.
That protein right there is specifically referred to as a, they have two names for it. There's many names for it actually. I'm going to write this protein up here.
This protein is called the dihydropyridine. receptor. Sometimes they even call it a voltage sensitive calcium channel. Sometimes they even call it the L-type calcium channels. I'm just going to refer to it as the dihydropyridine receptor.
And these are scattered all along the actual, this actual T-tubules membrane, which again, what is the T-tubule? It's an invagination of the actual sarcolemma. I'm not making that word up.
I know it sounds weird, but it is called invagination. All right. Anyway, These positive charges are moving across the actual t-tubule. As it moves across the t-tubule it stimulates this actual dihydropyridine receptor. What's really interesting is in the past they thought that the dihydropyridine receptor whenever it was stimulated due to this voltage it would open up a calcium channel and calcium would flow in.
They don't believe that that happens specifically in the skeletal muscle anymore. They believe that does happen in the cardiac muscle but not in the skeletal. Here's what they believe now. I'm gonna Take and just kind of zoom in on this picture right here just a little bit.
So let me get some of this out of the way. Let's say here I draw in purple. Here is my dihydropyridine interceptor. And then over here in pink is this other protein. And before I talk specifically about this protein, let me talk about what this big massive blue structure is.
Okay, so you see this big massive blue structure on both the sides of the T-tubule. This big massive blue structure is specifically called the sarcoplasmic reticulum. So again, this structure here is called the sarcoplasmic reticulum. It's basically just a specialized derivative of the endoplasmic reticulum, which is in most cells, right?
So the sarcoplasmic reticulum is really, really special because it's rich in calcium. There's a lot of calcium sequestered in this area. by a specific type of protein called calsequestrin.
We'll talk about him. Now, what happens is this sarcoplasmic reticulum are just tubes of this, like I said, kind of like an endoplasmic reticulum. Just tubes, and they're surrounding a lot of these T-tubules.
But here's the thing that's special about skeletal muscle. Usually, when you see these like big enlarged sacs of the actual sarcoplasmic reticulum, They technically call these large and large sacs of sarcoplasmic reticulum, they call it the terminal cisterna. Okay, so this would be a terminal cisterna, terminal cisterna, terminal cisterna, terminal cisterna. It's just the enlarged sac-like regions of the sarcoplasmic reticulum. Now here's what's really cool.
If you look here, skeletal muscle is really special. And the reason why it's really special is it usually always has a sarcoplasmic reticulum on... both sides of the t-tubule.
So how many things do we have here? We have two sarcoplasmic reticulums and a t-tubule in between. They call this whole structure here the triad. Okay, so what is this whole structure here called?
It's called the triad. And again, what is the triad? The triad is composed of the two sarcoplasmic reticulums and the actual intervening t-tubule or transverse tubule.
Okay, now we're going to talk about this. On the sarcoplasmic reticulum, you have this special type of protein. So again, what is this purple protein? It's called the dihydropyridine receptor. This pink protein is specifically called a ryanodine receptor.
And if we really want to be picky, type 1. Look what happens here. Normally this ryanodine receptor is specifically plugged in to the sarcoplasmic reticulum. So let's pretend that this blue here is the sarcoplasmic reticulum, right?
Now calcium is really, really rich in this area. So let's say here I have lots and lots and lots of calcium. And technically calcium is really rich in this area because it's bound by a protein called calsequestrin. We'll talk about that a little bit more in the actual next video. What happens is, whenever this actual dihydropyridine receptor is stimulated, remember, what was the actual dihydropyridine receptor embedded in?
It was embedded into the actual T-tubule, right? So this is the T-tubule membrane. Whenever those positive charges due to the voltage-gated sodium channels are moving across this dihydropyridine receptor, something really cool happens.
What he does is, he becomes special, and he develops, look. These things actually stick out a little bit more and they hook on to this ryanodine receptor. And when they hook on to the ryanodine receptor, they pull that ryanodine receptor out.
Now look what happens. When it pulls this ryanodine receptor out, what does that do to this actual point here of the membrane? It opens it up.
And then if it opens it up, what can start flowing out? Calcium. And when calcium starts flowing out, it can flow out into the actual sarcoplasm and start... binding on to what? It can start binding on to a specific component that you guys know as troponin inside of the actual sarcomere that we'll talk about.
So again, real quickly, let's review what's actually happening and then we'll see it in a larger macroscopic view. Specifically, this is the dihydropyridine receptor. It's located on what? The actual membrane of the T-tubule.
Okay, so now let's just review this real quick. This membrane here is the actual T-tubule membrane. In that membrane is the dihydropyridine receptor. Whenever this movement of positive charges, that action potential, due to the voltage-gated sodium channels are moving across this T-tubule membrane, it activates the dihydropyridine receptor.
The dihydropyridine receptor is normally mechanically coupled to this ryanidine receptor type 1, which is present on the sarcoplasmic reticulum's membrane. What happens is the dihydropyridine receptor, when it's stimulated by this voltage due to sodium, it holds on to the ryanodine receptor and plucks it out. When it does that, it opens up the channel for the calcium ions to start flooding out, okay, through this actual sarcoplasmic reticulum and inherent to the sarcoplasm.
So now, let's show that in just a really quick way to review. Positive ions are developing all the way around here, as the positive ions are accumulating all across this actual T-tubule membrane. which again is just an evagination of the sarcoplasmic reticulum.
What happens to these dihydropyridine receptors? They become active, they're mechanically coupled to this normal, this actual ryanidine receptor, and whenever they're coupled to this ryanidine receptor, what does it do? It pulls on the ryanidine receptor.
When it pulls on the ryanidine receptor, it creates a little pore that allows for what ions to start flowing out again. What's really, really rich in this area? calcium.
How do we actually keep calcium concentrated in this area? I told you one of them was due to a protein called calc sequestering. Another one is we have special pumps that we'll talk about afterwards that are also contributing to this.
Now once this actual brianidine receptor type 1 is pulled out what happens? Calcium starts flooding out and as the calcium starts flooding out what is going to happen to this calcium? This calcium that's getting pushed out of the sarcoplasmic reticulum, where's it going to go? That calcium is going to come all the way over here. And these calcium ions are really special because what they're going to do is they're going to come over here and they're going to bind onto a special protein called troponin.
And they're going to help to initiate what's called the sliding filament theory that we'll talk about in more detail in the next video. Okay. So you guys probably thought we're done. Unfortunately not.
We got one little last thing to do and then we are done. Okay. This is at the peak point. This is all happening.
while we're in this depolarizing action potential like current. Because again, it's all moving across the cell membrane, activating the dihydropyridine receptors, pulling the ranidine receptors, and releasing the calcium. Now, once we hit positive 30 millivolts, I already told you that it activates the, it stimulates the inactivation gate, which closes the sodium channels.
All right, you see this potassium channel over here, this blue channel? What is that little guy right there called? What do you think it is?
That's his activation gate. Whenever you reach positive 30 millivolts, that stimulates this activation gate. The communication gate will open. When the activation gate opens, what happens?
A special ion starts wanting to flow out. What is that special ion that wants to start flowing out? Potassium.
And potassium will start flooding out into this area. If we start pushing tons and tons of potassium out into this area, due to the activation, what am I activating again? I'm stimulating the activation gate. So again, what would happen to this one? When I reach positive 30 millivolts, I would open up.
This activation gate. When I open up that activation gate, again, what would start happening? Positive ions would start exiting the cell.
Think about this logically. As positive ions are being lost, and I'm talking, I'm not talking about just a little bit of potassium goes out, I'm talking a beastly amount of potassium is going out. Because potassium is in such high concentration inside of the skeletal muscle cell.
It's in such small concentrations outside of the muscle cell. That whenever potassium channels open, they start flooding out. And when these potassium ions leave, the inside of the cell is starting to lose positive ions. What starts happening to the inside of the cell membrane then? It's going to become very, very electronegative.
And potassium keeps moving out until it reaches its equilibrium potential, which is approximately about negative 90 millivolts. That's such a beautiful thing. That's resting membrane potential.
So look what happens here. I'm gonna have this come over like this. It doesn't have a plateau phase like this. Actually, so that we don't get this confused, let's get this out of the way, because I don't want you to think that there is a plateau phase. There is no plateau phase.
It comes like this and then goes down, and it reaches the point of resting membrane potential. Who's responsible for this? This is due to the potassium channels, okay? The potassium is leaving the actual cell.
So we call whenever the potassium is leaving a cell, we call potassium ion efflux. Whereas on this point over here, on this side, this depolarizing wave is due to sodium ion, sodium channels, and the sodium channels opening and sodium is flowing in. We call it whenever an ion is flowing in, we call it influx.
And again, This point here is referred to as depolarization, where the cell is becoming more positive, and then when it goes down to negative voltage, it's returning back to resting membrane potential. This is called repolarization. Okay?
Now, just to be consistent with these gates, let me expand on this gate a little bit more, because I don't want it to get too cluttered in here. Let's say I take this right here. Here's one part of the potassium channel, here's the other part of the potassium channel. And here, the activation gate was already open, and the inactivation gate is right here.
Okay, we said that the activation gate is activated whenever you reach positive 30 millivolts, the peak point of depolarization. Cool. But then, potassium keeps exiting the cell, and we said that potassium will leave the cell until what? It'll leave the cell until we reach resting membrane potential, which is almost exactly equal to his... equilibrium potential or his NERTS potential.
When potassium leaves and it reaches negative 90 millivolts, guess what happens to that inactivation gate? He becomes stimulated. So what voltage stimulates the inactivation gate?
The inactivation gate is stimulated by negative 90 millivolts. That'll stimulate the inactivation gate. Now let's show above what that'll look like so that we don't get this confused.
So as a result after this event, let's draw our blue channel again here. Here's our blue channel. Here's the other part of the channel.
Activation gate is like this. And then what happens is this actually blocks that point there. And then look, can potassium exit now?
No, he's repelled, right? And that happens there until we get to that point, right? So what happens is the inactivation gates will close.
And eventually, once the actual cell is at rest for a little bit, this inactivation gate will again, it'll open and then the activation gate will close. and then it'll wait for another stimulus and then the whole event will occur again. So now, to recap all this big beast that we did very, very quickly, what happens?
Acetylcholine is released. Acetylcholine binds onto these nicotinic receptors, specifically type 1. Generally, they're closed at resting membrane potential, which is negative 90 millivolts. Who's maintaining that?
The sodium potassium ATPases are maintaining that, as well as the potassium leakage channels. Once acetylcholine binds onto this receptor, it opens up the actual the actual nicotinic receptor channel. And sodium ions flow in, potassium ions flow out.
But more positive sodium ions are flowing in than these actual positive potassium ions are flowing out. Because of that, the cell is becoming a little bit more positive. As this cell becomes a little bit more positive, that develops what's called the end plate potential.
What does the end plate potential look like on the graph? Remember, it brings it from resting membrane potential up to threshold potential, which is negative 55 millivolts. When that reaches threshold potential, the voltage-gated sodium channels open, specifically the activation gate, right? It opens. It allows for the sodium to come in.
The sodium will keep flushing and flushing and flushing and flushing into this actual muscle cell and allow for the actual, the inside of the cell to become more electropositive. But it reaches a peak point of potential, which is around positive 30 millivolts. Once it reaches that point, the inactivation gate closes and sodium can no longer come in. Then, what happens also, just to continue on with the, let's go back to the activation part. Now, if this actual activation gate is still open, right, and the actual sodium ions are coming in, again, these positive charges will start moving along the actual sarcolemma, which is the plasma cell membrane, right?
And as it starts moving, along the actual sarcolemma, it moves down these invaginations of the sarcolemma, which is called the transverse or t-tubule. Adjacent to it, or to the sides of it, is usually two sarcoplasmic reticulums. These big, basically derivatives of the endoplasmic reticulum. And they're nice calcium storage factories. These together, this sarcoplasmic reticulum, this sarcoplasmic reticulum, and this t-tubule make up the triad.
These enlarged sacs are called the terminal cisterna. What happens is as the actual action potential moves down the actual t-tubule, it stimulates the dihydropyridine receptors, which are mechanically coupled to the ryanodine type 1 receptor. Whenever it's activated by this voltage, it pulls on the ryanodine receptor and allows for the calcium ions to start flowing out of the sarcoplasmic reticulum and into the sarcoplasm. And then where does that calcium go?
It goes over here to the sarcomere and binds onto troponin to initiate the sliding filament theory. Then... Every cell has to rest. So we were at the peak point of depolarization. What happens?
If you guys remember, the potassium channels have an activation gate that are opened whenever it reaches peak potential, positive 30 millivolts. Potassium starts rushing out of the cell. It'll rush out of the cell consistently until it's reached a specific point of nurse potential, which is when the inside of the cells become negative 90 millivolts, approximately. When that happens, when the potassium ions keep leaving and it reaches this point of about negative 90 millivolts, the inactivation gate is going to start, where did we draw that, right here?
Whenever we reach negative 90 millivolts, the inactivation gate is going to start closing. And whenever that closes, again, potassium can't leave out. But then again, eventually the inactivation gate will go back and the activation gate will close. And it will wait for another stimulus to occur for that event to happen. Alright.
We covered a boatload of stuff in this video. I thank you guys for sticking in there with me. I really hope it made sense, guys.
I hope you guys did enjoy it. In the next video, in part three, we're going to specifically look at the sliding filament theory and how this contraction is coupled with this electrochemical excitation event. All right, Ninja Nerds, I will see you soon.