Increasing ventricular contractility - inotropic effect

I'm going to start out by showing you the membrane potential of a cardiac cell. And I know you've seen this a few times now, so you might be getting kind of tired of it. Or it might be seeming kind of familiar, and that's good. That's good that you know this by now. But let's just go over it just in case you need some refreshing. So if you have a heart muscle cell, and let's just make sure that we're totally on the same page, this is a heart muscle cell, or a myocyte. If you have one of these cells and you're looking at it, usually it kind of hangs out in a negative membrane potential. Meaning the cell is negative relative to its environment. And it kind of hangs out there for awhile. And then we know that at some point, it's going to get some positive charge from a neighboring cell. It's going to have an action potential. It's going to go really positive, and then it's going to peter down a little bit as the potassium channels let out potassium. And then it's going to go through this kind of interesting plateau where calcium is rushing in, potassium is rushing out, and finally, it kind of goes back down as potassium wins the game. And potassium kind of drives it back down to its kind of happy place where it likes to be. Around negative 90 or so. So these are the phases of an action potential. And we know that they're numbered off. This is phase 0, or 4 rather, phase 0, and this is 1, 2, and 3. So these are the normal phases and how we count off what it would look like. And what I want to do now is draw your attention to the heart. And let's not lose sight of what the whole organ looks like. And this is our four-chambered organ, this is our heart muscle. With the two ventricles down here and our two atria up top. And this is our right atrium, left atrium, right ventricle, and left ventricle. So this is what it looks like, right? And there are actually nerves that come and sit on different parts of this. So there's a nerve that might come and sit right there. And this might be a parasympathetic nerve. I'll write P for parasympathetic. And actually, parasympathetic nerves also come over to the left atrium. They settle in on left atrial tissue as well. And you also have sympathetic nerves that come and settle in over here and on the other side as well. Now as far as the ventricles go, you really only have sympathetic nerves down here. So that's an interesting thing, and I wanted to point that out to you. So you really only have sympathetic nerve stimulation. You don't really have much parasympathetic activity down here. So I'm going to focus in now. The rest of this video is actually going to just focus in on the ventricles. I'm actually going to just kind of ignore what happens in the atrium because the main point I want to make is that sympathetic activity on the ventricles is going to cause increase contractility, meaning you're going to be able to cause increased force of contraction. And why do I not care as much about the force of contraction of my atria? Well, it's because the atria are going to be used to help fill up my ventricles. But my ventricles, the force of contraction in my ventricles is really important because that's going to affect how the blood gets to the rest of the body and to the lungs, and so that's why I want to focus in on just the ventricles for the rest of this talk. Now, I'm going to draw a ventricular cell. So this is a ventricular muscle cell. Let's say it's right here. This is this little guy over here where the x is. So this ventricular cell-- I'm actually also going to even be more specific, I'm going to focus in on what happens in phase 2 and 3 of this cell. So our ventricular cell, it's going to, in phase 2, have some channels. It's going to have some potassium channels. Voltage gated. Potassium leaving. It's going to have some calcium channels. Some voltage gated calcium channels letting calcium in. And you remember, actually, when that calcium comes in, we talked about the fact that there's this sarcoplasmic reticulum. This is our sarcoplasmic reticulum. And this sarcoplasmic reticulum is kind of a bag of calcium. And so the sarcoplasmic reticulum is going to wait patiently for a little calcium to come and bind to its channel. And the moment it does, it's going to start letting calcium out. So this thing is full of calcium. And it's going to start shooting into the cell. Into the kind of cytoplasm of the cell. So these are kind of the changes that normally take place in phase 2 and 3. You have calcium rushing in, and you have the sarcoplasmic reticulum dumping calcium out. And you also have-- when I say out, out into the cell-- and then you also have potassium actually leaving the cell entirely. Now, if you have sympathetic nerves. Let's say this is my sympathetic nerve. I'm going to write S for sympathetic. Well, maybe I'll just write it out just to make sure that we don't have any confusion. This my sympathetic nerve. My sympathetic nerve is going to have-- let me make a little bit of space here-- is going to have some neurotransmitter in this kind of space in here. And that's going to bind to a receptor. Now a receptor is going to send a message into the rest of the cell. And this neurotransmitter that's doing the messaging, and we actually-- I almost switched it. I was going to write acetylcholine, but what I mean to write is norepinephrine. And acetylcholine, just as a point of reference, is the neurotransmitter that the parasympathetic nerves use. So I want to make sure I don't screw that up. So norepinephrine goes into the cell, and what does it do? Well, it's going to cause an effect here. It's going to make the calcium rush in even more forcefully. It's going to activate these channels so that they let out more calcium when they get a chance to do that as well. And so these are two major changes, right? It's going to activate more calcium coming in or basically activate these channels so more calcium can rush in. And it's going to let more calcium out of the sarcoplasmic reticulum. So my curve is going to start looking like this. Calcium is going to make this rise. It's going to rise because remember, calcium wants the membrane potential to go up. And the reason that it goes down, eventually, is because of potassium. So if you have more calcium rushing, it's going to quietly start winning the battle. So it won't be a plateau anymore. It'll start kind of looking like I just drew it. Now a second thing that happens with sympathetics, and this is actually very interesting, is that you have these ATP controlled channels or proteins, really, that allow calcium back in. So these are transporters that are going to get calcium to come back in. And of course, this is going to happen when the sarcoplasmic reticulum is ready to kind of mop up all the calcium and let it reenter the SR, the sarcoplasmic reticulum. So when that's happening, usually you get a decline like what I've drawn in phase 3. But if you're going to stimulate that, and that's exactly what happens, the sympathetics kind of stimulate that, well, all of a sudden now the calcium can get quickly put back into the sarcoplasmic reticulum. And if it quickly goes back inside, then the calcium current falls more rapidly. And the potassium current dominates even more than it usually does. So basically, what happens is instead of having kind of a slower phase 3, you have a rapid phase 3. And that is because of the fact that you're able to get the calcium more quickly and more efficiently tucked into the sarcoplasmic reticulum. So at the end of the day, you see some interesting things, right? You see that you're able to quickly get back to baseline. And as a result, this distance goes down. So you actually have a smaller contraction in the sense that-- let me rephrase that completely so I don't confuse you-- you don't have a smaller contraction, you have a shorter, in terms of time, contraction. But you have more calcium that's actually coming into the cell. So these are two key changes I want to point out to you. The fact that you have more calcium coming in, but it's a shorter period of time. So those are the effects of the sympathetic nerves on the ventricular muscle cells. So you can see now that you're going to have a change in inotropy. And inotropy just means a change in force of contraction or affecting the force of contraction. And here we're talking specifically about the ventricles, but those are the chambers I said that we care more about in this scenario. And so inotropy is really shown to be affected right there. So you can see right there, you have more calcium, and more calcium means more force. So more force of contraction. And that's because calcium actually directly affects the mechanism that a cell uses to contract. And we'll talk about that in future videos, exactly what that mechanism might look like. But really, that increase in calcium is a demonstration of the inotropic effect of a sympathetic nerve. And this effect is actually showing you that the ventricles can repolarize more quickly. So this is more, let's say, rapid ventricular repolarization. So that the ventricles are actually kind of reset and ready to fire again more rapidly. Rapid repolarization. So these are the two major sympathetic nerve effects on the ventricular muscle cells.