Contractility

Transcription

Something that I really, really enjoy doing-- and I've done it a lot-- is camping. And so I'm going to start by telling you a little story of a recent camping trip. And I like to, in the morning-- let's say around 9:00 AM-- head down to the river. It's always kind of a fun thing to do. And so this day was no different. I went down to the river feeling good and had a big smile on my face. And what I want to do is think about that moment. In fact, if we had stopped time around 9:00 AM as I was down by the river, what would you see in my heart? What would you have actually noticed? Now, the heart has, of course nerves, leading up to it, so we've got sympathetic nerves. And these sympathetic nerves at all times are releasing some amount of their neurotransmitter. And the neurotransmitter's, of course, just some chemical that helps communicate a message. So this is my neurotransmitter, and I'm going to name it norepinephrine, which is the one that this particular one will be releasing. And so the norepinephrine is headed from the nerve. And it's headed over to my heart cell. And so, of course, my heart cell, it has little receptors on the surface. And let's say that of these three receptors, one of them gets the signal. And this guy right here releases now the signal in this heart cell. And of course, calcium is going to come into the heart cell. And we've talked previously about exactly how that happens, but you know that that happens. And if that calcium gets into the heart cell, which here it does, where is it going to go? Well, you have, of course, muscle proteins-- myosin, actin-- in that heart cell. And those muscle proteins are going to basically require a little bit of calcium in order to work properly. So this is my myosin. And let me now draw some actin. This is actin protein. And this actin I'm showing in kind of a crunched situation. This actin is kind of crunched together. And when I say crunched, I basically mean that there's very little room, because this is going to be the end of systole. Let's just assume that we're at the end of systole here. I'll write that here. End systole. So it turns out that, I guess, when I froze time at 9:00 AM, it happened that I caught this magical little time point-- end systole. And some of that calcium is, of course, binding to troponin C. And I'm just going to scatter some calcium randomly, so I really am not putting too much thought into exactly where it goes. But it's kind of throwing it out there. And now our question is going to be how many myosin heads are actually working. And I'm going to circle the ones that are working in red. So this one is working because it's close to actin. And there's calcium on there, and it's the right polarity. But the next one over, this one, I'm not going to circle because it's the wrong polarity. This one has calcium that's too far. It's on the wrong side. And this guy-- well, this guy actually would be circled because he's got calcium on the right-polarity actin. This guy I would circle as well for the same reason. And these two I cannot circle because they're the wrong polarity. But this one I will circle. So we've got about 4 out of 20 that are working. And I could actually just rewrite that as 4 out of 20 works out to-- what? 20%. So 20% of my myosin heads are working. So that's not great, but it's not awful, either. So to sum this up, at 9:00 AM I was walking along the river. And at that time, at the end of systole, if you actually wanted to see how much of my myosin was actually working, you'd say 20%. Now that night, 9:00 PM, an interesting thing happened. I also headed out, went outside. And wanted to do one last little look around. And I encountered a scary animal, a scary beast, I would even say. And this animal had four legs-- and let's see if you can recognize it-- had a striped tail and a striped body. And this horrible, horrible little creature is none other than a raccoon. So this is my little raccoon with a ugly little face. And this raccoon, like many raccoons do, scared me. And you should know, I do actually in fact have a fear of raccoons. And so this was a very scary event for me. I shrieked, and I was not too happy. So what was going on in my heart at that time? Let's actually do a little cut-paste job. All right, so now I'm basically just going to try to cut and paste some of this, and I'll erase the parts that are not relevant. So I've got something like that. And let me just quickly erase the parts that I know I'm not going to want. So let's start there. I've got my sympathetic nerves that are now going to be going crazy. I'm going to just draw a giant arrow because they are going to be driving a message down there saying, hey, this raccoon is awful and scary. Let's just get lots and lots of neurotransmitter released. So they're going to just release tons and tons of neurotransmitter. And that is an important issue. This is how signals get passed. And so, of course, now all of my receptors are jamming that signal. And of course, that signal means that calcium is going to flood my cell. All of a sudden, I have much more calcium in my cell than I used to, tons and tons of calcium. And in fact we know that this is the key way that our nerves are able to communicate a message. They basically help by sending ions into cells. So now our cell is jam-packed full of calcium. And so now I can just kind of scatter calcium everywhere, just kind of sprinkle it all over the place. And let's see what happens now. So I've got calcium everywhere. And same question as before-- how many myosin heads, rather, are going to be working for us. So let's just circle the ones that are working for us. We still have a few that are not going to be working because they're blocked by the wrong-polarity actin. But these are actually now all recruited. All of these are. And on the other side, I've got some recruitment over here. So I've got lots and lots of myosin heads recruited. I've got-- let's see if I can count it up-- 5, 10, 11, 12. So I've got 12 out of 20. Or that works out to 60%, so 60% up from 20%. I'm going to make a little bit of space on our canvas now. But just kind of think about that, the fact that at 9:00 AM in the morning my heart, at the end of systole, was cranking out at 20%. And now it's working at 60%. So what does that mean exactly? How can we put that together in an image that we can kind of remember and think about and make sense of? So for this part, I think it would be helpful to go back to our pressure-volume curves. So we've got this idea that at the end of systole, we have a relationship called the end-systolic pressure-volume relationship. I'm actually going to draw it out here. Something like that. This is a sketch of our end-systolic pressure-volume relationship. And we know-- and yellow will be our 9:00 AM. Let's just kind of keep that in mind. This is what was happening in the morning as I was relaxed. And at the end of systole, I said we had about 20% of our myosin heads working. So if I was-- let's just take a spot here, and I could take any spot. I'm just choosing it randomly. And let's say this is the volume at that spot. And if I fill it in with blood, it would look like that. And at this point, we've got our workers. Remember, our workers represent how much force of contraction there is. So our workers are yanking this way and that on this rope. And our worker-- I'm just going to quickly sketch out-- maybe looks like that. And we've got another worker down here-- long arms, apparently. And if I was to look at my workers' faces-- because I've drawn the faces very, very small, it's hard to see them-- they're yanking. It's not like they're-- they're not lazy. They're not just standing there. But they're yanking, and this is the face of someone that's working, let's say at 20%. Now, at that same moment, let's say instead of yanking at 20%, let's say I yanked at-- I don't know-- 60%. Just to make it kind of the same as the other one. If I was yanking at 60%, well, now I would actually create more pressure. So same volume. And I'm actually going to just kind of sketch higher-- maybe something like this. So at that same volume, it would basically look like this. And I've going to try to draw the exact same volume so you believe me. This is, let's say, the same volume-- about the same, anyway. And here, let's fill it up with blood. We've got our two workers doing kind of the same thing. We've got workers yanking on this left ventricle. And these workers are working much harder. So they're working much more diligently than previously. And they're yanking, of course, same directions, opposite from each other. And these workers, if you were to stare at their face, you'd notice they're really into it. They're really, really trying to-- grr. They're really, really trying to pull apart on that left ventricle, And as they are working so much harder-- and actually, maybe I should even write the percentage in here. Let's write 60% here. They're working so much harder. What that does is for any given volume, the same volume, they're going to have a much higher pressure. So these are going to be able to drive a higher pressure. And that's what you see, right? This volume is the same. I've tried to sketch it to be the same, but now you can see it's the same exact point. And yet the pressure is much higher. Now, going back-- and this is, of course, our 9:00 PM. This is when I was scared. This is my 9:00 PM sketch. Now, going back to the 9:00 AM, the morning sketch, let's say I was to pull a little bit of volume off of my heart. Well, the pressure would fall, and it would keep falling. And so remember, this is how we even created this line in the first place. And it kind of ends down here. And at 9:00 PM in the evening, I could do the exact same thing. I could say, well, if I drop the volume a little bit, I'll get a lower pressure. And if I drop the volume again, I'll get at a lower pressure. And it eventually also heads down to the same spot. Because remember, you do need a minimum amount of volume, some minimum amount, to be able to even generate pressure. And that's going to be the same minimum amount for both of the situations. So you need that same minimum amount. But as you go higher from that point, you actually go along a different slope. And so really what you're creating is two lines of a different slope. And the difference is really reflected in our percent work. So our 60% line is different from our 20% line. And I could even test you. I could say, well, what if I was to draw a line? I'm going to just make a little bit of space now. What if I was to draw a line somewhere in the middle? What if I drew a green line that looked like this? What would be your guess as to what percent work that is? And you would say, well, you know, it looks like something between 20 and 60. I don't know-- maybe 40%. So this would be your guess just by looking at the line. So what you're saying, or what I'm saying, really, is that you can change the slope of the line up or down. And what that reflects is how hard your muscle is contracting. And that goes back to the myosin heads that you're using to contract. And so what this really means, the slope of the line in these three lines that I've drawn here, really reflect an idea called contractility. And you'll see contractility mentioned all the time. And all it really means is the slope of that line. And you can change the slope of the line. The main way is through calcium. So calcium-- more or less calcium-- changes the slope of the line. And remember, that's how our sympathetic nerves work. So this is kind of the main way that our sympathetics change or affect that line. Sympathetic nerves. And finally, I want to make sure that you don't get the idea that that's the only way to change contractility. You can also change the pH, or you can change the temperature-- all of these things will affect how well myosin can work. Because of course, myosin is a protein, and proteins need an ideal pH or temperature. But I mentioned that just so you know that. But truthfully, the one that we always seem to talk about or always think about is this one. And the main reason is because that's something that our sympathetics have gotten so good at controlling.