Action potentials in cardiac myocytes

Let's figure out how a heart squeezes, exactly. And to do that, we have to actually get down to the cellular level. We have to think about the heart muscle cells. So we call them cardiac myocytes. These are the cells within the heart muscle. And these are the cells that actually do that squeezing. So if you actually were to go with a microscope and look down at one of these cells, it might look a little bit like this, with proteins inside of it. And when it's relaxed, these proteins are all kind of spread apart. And when it's squeezing down, because each cell has to squeeze for the overall heart to squeeze, these proteins look completely different. They're totally overlapped. And that overlapping is really what we call squeezing. So this is a squeezed version of the cell. And the first one was a relaxed version. And the trigger that kind of gets it from squeezing-- and of course actually, I should probably draw that too. The fact that, of course, at some point it has to go back to relaxed to do it again, to beat again. But the trigger for squeezing is calcium. So it's easy to get confused when you're thinking about all this kind of squeezing relaxing all this kind of stuff. But if you just keep your eye on calcium and think about the fact that calcium is the trigger, then you'll never get confused. You'll always be able to kind of find your way in terms of where the heart is in its cycle. So I'm going to draw for you the heart cycle, and specifically the cycle of an individual cell. This is what one cell is going to kind of go through over time. And the heart cycle, or the cycle for a cell, a heart cell, is going to be measured in millivolts. We're going to use millivolts to think about this. And you could use, I guess, a lot of different things. But this is probably one of the simplest things to kind of summarize what's happening with all of the different ions that are moving back and forth across that cell. Now the major ions, the ones that are going to mostly influence our heart cell, are going to be calcium, sodium, and potassium. So I'll put those three on here. And I'm putting them really just as benchmarks just so you can kind of keep track of where things would like to be. So calcium would like to be at 123 millivolts. Sodium at 67. And what that means is that if these were the only ions moving through, then sodium would like to keep things positive. And potassium, on the other hand, would like to make the membrane potential negative. So this scale is actually the scale for the membrane potential. And if we move up the scale, if we go from negative to something positive, this process would be called depolarization. That just means going from some negative number up towards something positive. And if you were to do the reverse, if you were going to from something positive to something negative, you'd call that repolarization. So these are just a couple of terms I wanted to make sure that we're familiar with, because we're going to be able to then get at some of the interesting things that happen. I'm going to make some space here inside of this cell. So let's start with a little picture of the cell. So let's say that this is our cell here. And I'm going to draw in little gap junctions, which are little connections between cells. So maybe a couple there. Maybe one there and maybe one over here. And let me label that. So these are the gap junctions. And also let's draw in some channels. So we have, let's say, a potassium channel right here. We know the potassium likes to leave cells. So this is going to be the way that potassium's going to flow. And it's going to leave behind a negative membrane potential, right? And let's say potassium is the main ion for this cell, which it is. Then our membrane potential is going to be really, really negative. In fact, if it was the only ion, it would be negative 92. But it's not. It's actually just the dominant ion. So it's over here and our membrane potential is around negative 90. And it continues around negative 90. So let's say nothing changes over a bit of time. So we stay at negative 90. So this is what things look like with the dominant ion that our cell is permeable to being potassium. Now a neighboring cell, let's say now, has a little bit of a depolarization. So it goes positive and through the gap junctions leak a little bit of sodium and some calcium. So this stuff starts leaking through the gap junctions, right? Now what will happened to our membrane potential? Well it was negative 90, but now that we've got some positive ions sitting inside of our cell, our cell becomes a little bit more positive, right? So it goes up to, let's say, here. And it happens pretty quickly. So now it's at negative 70 up from negative 90. So at this point, you actually get-- I'm going to erase gap functions-- but now that you're at negative 70, you actually get new channels opening up. And I haven't drawn them yet, and I'm going to erase sodium and calcium just to make some space. But you get new channels opening up. And these are going to be the sodium channels. So let me draw those in. Sodium channels. And there's so many of them. Lots and lots of these fast sodium channels open up. And I say fast because the sodium can flow through very quickly. So the sodium starts gushing in. And you know that's going to happen because there's a lot more sodium on the outside of a cell than the inside of a cell. And so sodium gushes in, and it's going to drive the membrane potential very quickly up to a very positive range. Now it would go all the way, let's say close to 67, maybe not exactly 67, because you still have those potassium ions leaving. But close to it, if not for the fact that these voltage-gated channels actually close down. So these sodium channels are voltage-gated. And they will actually close down just as quickly as they opened up. To show that, I'm actually going to do a little cut paste. I'm going to just draw this cell here. And I'm going to move it down here. So we've got our cell just as before. And now these voltage-gated channels, they close down. So let me get rid of all these arrow heads. But we're already now in positive range. So at this point, you could say our channels have caused a depolarization. And let me just quickly show these shut downs so that you don't get confused. There's no more sodium flowing through. You still have some potassium leaking out, but that's kind of as it's always been. And in addition to those potassium channels, that little channel I've drawn here, you have new potassium channels that open up down here. And these are actually voltage-gated potassium channels. So you had them before. They existed. But they were actually not open. So let me just draw little x's. And the only reason they flipped open is because the depolarization happened. You had a negative go to a positive. So now that our cell is in positive territory, actually let me write in positive 20 or so, our potassium voltage-gated channels open up. So these voltage-gated channels open up. And you can guess what's going to happen. Like which direction do you think that the membrane potential will go? Well, if the sodium channels aren't gushing the sodium inwards and potassium is leaking outwards, now you're going to have a downwards repolarization. So now potassium is causing the membrane potential to go back down. And let's say it gets to about positive 5. And if it continued, again, it would go all the way back down to negative 90. But an interesting new development occurs. At this point, I'm going to actually cut paste again. And I'll show you what happens next, which is that calcium-- this is the thing I said keep your eye on the whole time, right?-- calcium finally kind of starts leaking in. So let me get rid of this. And this is the key idea, right? I don't want to forget that this is potassium. So you still have potassium in the same over here. But now calcium leaks in. And let's draw that over here. So you have these calcium voltage-gated channel that allow calcium to come it. So you've got calcium coming in, potassium leaving. Now think about what will happen in this situation. So calcium is going to want to rise the membrane potential this way. Potassium leaving is going to want it to continue going down this way. And because both are happening simultaneously, you basically get something like this. You get kind of a flatline. So because both events are happening, both potassium leaving the cell and calcium entering the cell, you get this kind of flatline. And the membrane potential stays kind of around the same. And so it can just write something similar, something like positive 5. Just so we're clear, these are also voltage-gated calcium channels. So to round this out, then what happens after that? So you have so far, so good. We have all these channels coming in to our cells and allowing different ions passage. And now we get to something like this. And I'm going to try to clean this up a little bit. And what happens is that the calcium channels actually close just as suddenly as they opened. So now you don't have any more calcium coming in. And if calcium was the only thing that was keeping this membrane potential going flat-- you know, I said that the potassium makes it want to go down, but the calcium was making it flat-- well, what will happen now? Well, if again you have just those potassium channels open, well then you're going to have the membrane potential go back down. It's going to go back down to negative 90 or so. So this is kind of the last stage, where those potassium channels are going back down. And those voltage-gated potassium channels also close at this point. So finally, they close down as well. And so now that they're closed, you're going to finally get back to just your initial state, which was having a little bit of potassium kind of leaking out of this cell. And those voltage-gated channel have shut down now. So now that you're at negative 90, you stay down there. And this process is ready to begin again. The last thing I want to say is the stages, how they're named. So this is state four, this kind of baseline negative state that the relaxed muscle cell is. And then this action potential, when it finally fires and it hits that negative 70, this is actually considered a threshold. This is our threshold. When it gets to that point, we call that stage 0. And then on the other side of stage 0 you have stage 1, 2, and 3. So stage 1 is that point when just the potassium channels first open up, the voltage-gated ones. And then stage 2 is when they're balanced with the calcium channels. And stage 3 is again when you have just potassium channels, voltage-gated ones that are open. And then you get back to stage 4 again. So this would be stage 4. And because stage 0 is happening so rapidly, because this is so fast, we actually call this a fast action potential. So compare that to how the action potential goes in the pacemaker cells, where it's much slower. This fast action potential is a result of those really, really amazingly quick voltage-gated sodium channels.