Health and medicine
- Why doesn't the heart rip?
- What is preload?
- Preload and pressure
- Preload stretches out the heart cells
- Frank-Starling mechanism
- Sarcomere length-tension relationship
- Active contraction vs. passive recoil
- What is afterload?
- Increasing the heart's force of contraction
Find out why stretching a heart cell in diastole affects how forcefully it contracts in systole. Rishi is a pediatric infectious disease physician and works at Khan Academy. Created by Rishi Desai.
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- How does troponin C sense stretching? Surely for it to do that it must be attached to both ends of the cell.(9 votes)
- I'm just speculating, but it is probably feeling the stretch because it is attached to tropomyosin, which is wrapped all around actin from end to end. If actin is stretching, so is tropomyosin and so is troponin (C).(7 votes)
- Are these two mechanisms the same in skeletal muscle, with the preload being an eccentric movement prior to concentric?(5 votes)
- With skeletal muscle, lengthening a muscle fiber is eccentric whereas shortening a muscle fiber is an eccentric contraction. If one were apply the principle of preload to skeletal muscle rather than cardiac muscle, one might think of preload as plyometrics in athletic performance training.
In athletic training, the idea behind plyometrics is to slightly lengthen a target muscle (i.e. eccentric) in order to generate a more powerful concentric counteraction. Plyometrics is analogous to what is happening with the Frank-Starling principle in the sense that they are both relying on a stretching of the muscle fiber to generate an increase in force.
Keep in mind that the sarcomeres of skeletal muscle fibers have an ideal length at which they generates the maximum amount of force. If a muscle fiber is stretched beyond its optimum point, its force production capability diminishes rapidly. Additionally, the length-tension relationship varies according to the type of muscle fiber (e.g. skeletal vs. cardiac) being considered. Of note, the sarcomere length that generates the maximum amount of force is signficantly higher for cardiac muscle than for skeletal muscle. See here: http://files.slidingfilament.webnode.com/200000029-0c3dd0cbbf/lengthtension_compare.jpg(4 votes)
- Is it correct to say that Tropinin C in a stretched myocyte has "higher affinity" for Calcium, as opposed to Troponin C in a myocyte that is not stretched?(2 votes)
- If preload is equal to wall stress at the end of diastole, then how come wall stress is being multiplied by other things in the equation?(2 votes)
We talk a lot of pressure, and I thought it would be kind of a neat exercise to go through what exactly is the point behind the pressure? Why does it matter so much what the end-diastolic pressure is? And that's what that "ED" means. And to do that, I think one of the best ways is to just say, well, what happens if we change it? What would be the result of changing the pressure at the end of diastole? The first change that you would see is-- you remember there's that equation around preload equaling-- we know the pressure at the end of diastole times radius at the end of diastole. And of course, then if pressure goes up, then preload would go up. And we know that wall thickness times 2 is in the denominator. So the first thing I would say is, well, if you say pressure goes up of if that's our assumption, then we have to assume that preload would go up as well. That's the next thing. Well, you might say, OK. Well, let's take it a step further. So what? That preload goes up. How does that change anything? Again, I think it's helpful to kind of think about what preload is, and then some things will become very, very obvious right away. If we look at a cut section of the left ventricle-- this is my left ventricle. And I've kind of sliced through it. Then, you know you've got pressure kind of hanging out in here. This is our end-diastolic pressure-- the same thing we started with. Right? Pressure at the end of diastole. And if you increase that pressure, then you know you're going to cause some changes around the walls. You're going to have wall stress. And we know that wall stress and the end of diastole we call "preload." So basically, these yellow arrows represent preload. And in fact, I might even point out to you that, if I actually zoomed in, there would be a little red cell, like a little square-ish. And that little red guy, that little red cell-- let's draw him over here-- he's actually going to literally start feeling the effects of stretch. So he's hanging out nice and happy. And all of a sudden, this little fella is going to get stretched. He's going to start looking like this. And I don't think he would be upset. I think he would look just as happy, but he might look like that. All stretched out. His eyes stretched away from his smile. So this is what our cell will begin to look like if we continued to stretch. And the reason is because you're literally yanking on the two sides. Right? So that's what becomes of this process. This causes the cells to almost look like little pancakes. I say pancakes just because I enjoy pancakes so much. But just remember that the cells flatten out and they stretch out. And that's a direct consequence of the increased preload. So this causes increase-- I'm just going to write "stretching." In fact, maybe I should even say "stretching of heart cells" just so we don't forget exactly what we're talking about. So stretching of heart cells. And you could literally imagine it. Right? You can imagine these little cells getting stretched out. And you can also imagine-- if you think for a moment-- of all of the contents of the cells getting stretched out. So stretching actually stretches out, not just the cell itself, but everything inside the cell. And a few interesting things begin to happen when all of the proteins inside of a cell get stretched out. There are two important things that happen with stretching. And now we're getting into kind of the meat and potatoes of increased pressure, what it causes. So the stretching itself is going to happen. I think that part you can kind of reason through that and kind of assume that that make sense. And one thing that it causes is what we call the "Frank-Starling mechanism." Obviously, named after two folks named "Frank" and "Starling." And the Frank-Starling mechanism-- we'll actually get into some details about this separately-- but the Frank-Starling mechanism, put simply, is going to be something like this. I'm going to draw another myosin and actin. So remember, myosin has got these fantastic little myosin heads always looking to work. Right? They're always looking to bind actin, and they're on both sides. I'm going to just draw it here. So here in purple is just myosin bit. And I'm going to actually cut and paste this and show you what it could look like on the side. I'm going to draw two versions, and we're going to start seeing how the Frank-Starling mechanism how it makes sense. So we've got this actin kind of sitting here, and it's on both sides. Right? So it's going to be on both sides. In this first drawing, I've drawn things very crowded. There's a lot of crowding happening there. And so you basically get these areas where-- for example, let's draw it here. These two myosin heads. And these two myosin heads are literally being blocked by this actin. So for example, these two myosin heads are being blocked by that actin, and these two are being blocked by that actin because they would both like to be on their other side. Right? They would like to be binding to that actin, and this set would like to bind to that actin. So you've got actin crowding out other actin, which sounds kind of funny because you think, well, so what? How come the myosin doesn't just simply bind the actin that's closest to it? Right? That seems like an obvious solution. But in fact, actin has a polarity. It can only really bind in one direction. So when things actually get crowded, that becomes a major problem because now myosin literally can't get to the actin with the correct polarity-- as you see in the first diagram. So what happens in the Frank-Starling mechanism is that, when you stretch out your heart cell, you're also stretching out-- as I said-- all the proteins within. And now you've got a lot of happy, happy myosin heads. These guys are happy. Right? These guys are happy, and these guys are happy as well. So basically, what you see is that, by stretching things out, you could actually get more myosins back on the job. And so that's kind of the key with the Frank-Starling mechanism-- you have more myosin heads at work. This is a key point. And there's some nuances to it. I've kind of simplified the Frank-Starling mechanism. There's some important nuances we'll get into-- as I said-- later, but this is one of the key elements of it. And the other stuff stretching-related mechanism is called an "inotropic mechanism." And usually, when you think of inotropic you're probably thinking that it has something to do with calcium. And you're right. Inotropic does have to do with calcium. And what it means is that basically-- let me, actually, give a little bit more space. If we were to zoom in now-- remember, we have our actin and myosin. And you know how valuable it is to have the two binding to each other. So you have something like this where your actin is there, and let's say you've got a mysosin here hoping to bind to it. This is our myosin. Then, what you see is that the actin is guarded by what? It's guarded by tropomyosin, Right? That's the protein that's kind of acting like a chaperone making sure that the myosin and the actin don't interact. This is our tropomyosin. Again, you can think of it as a chaperone just protecting that actin. And the thing that's going to help us move the tropomyosin out of the way is none other than our friend troponin. So this is our troponin, and troponin is going to scooch the triple myosin away. And troponin comes in three protein bits, and we call them "Troponin C," "Troponin I," and "Troponin T." And it's the Troponin C that I'm going to focus on for right now. So in the Troponin C, let's say it's looking like this. Right? This is our Troponin C. Remember, it's going to potentially bind to calcium. In fact, it will bind to calcium. This is my calcium. Right? So this is my Troponin C and my calcium. When things are stretched out-- so when things get stretchy, I'm going to say "stretched"-- well, the proteins feel that. And the Troponin C is going to look stretched. It's going to look like that. So this is my Troponin C all stretched out. And Troponin C-- the stretched-out version-- literally behaves slightly different than the Troponin C when it's not stretched out. Troponin C when it's not stretched out is thinking to itself, well, eh, maybe I can bind calcium. Maybe not. I'm not particularly plussed either way. So it's thinking, eh, maybe I don't want to bind calcium. Maybe I do. But the Troponin C that's stretched out is saying, yes, please. Let's bind. So it's screaming to bind with calcium. So that's a big change, isn't it? Because if Troponin C wants to bind calcium-- and that's exactly what happens when things get stretched out, is that Troponin C kind of changes its shape, and now it really wants to bind calcium. If that happens, then all of a sudden, the Troponin C is going to be more effective at getting tropomysin out of the way. And myosin can now bind actin. So let's recap these two mechanisms. They have a lot to do with each other. Right? So when things stretch out, the Frank-Starling mechanism allows more myosin heads to get to work. And the inotropic mechanism basically is kind of a change in the way that Troponin C's shape is, and that change in shape makes it want to bind calcium very eagerly. So let's put it together. You've got more myosin heads at work. That's what Frank-Starling taught us. And as far as the inotropic mechanism, you may not have more calcium, but what calcium you do have is going to have a bigger effect because the Troponin C really wants to bind to it. Calcium has a bigger effect. So if you think about them, you've got more myosin now. And the calcium is obviously going to help the myosin bind to actin more easily. So putting it all together, you're going to basically get more myosin burning up ATP turning it into mechanical force or mechanical energy. So the end result of all this is that you have a larger mechanical force. I'll say left ventricular force of contraction. So this is kind of the end of the day what you're going to get. And as you get that larger force of contraction, I could go even further and say, well, what is that force? Well, it's pushing against blood, and that's pushing out on a certain area. And force over area is pressure. So a larger force of contraction really translates into-- what you're saying is-- a larger left ventricular pressure. And this-- just to be very, very clear-- is going to be during systole. So we started talking about diastole. Right? The question was-- what the heck is the point of knowing about preload and end-diastolic pressure? And the point is now very, very clear. Right? Because if you can have a higher preload set up the stretching of heart cells, that's going to cause two mechanisms to start changing the way that molecules within those heart cells are working. Right? The actin and myosin is actually going to be able to bind more easily to each other. And also, the calcium has a bigger effect-- kind of freeing up the actin. And at the end of the day, you get this larger left ventricle pressure during systole. So really, diastolic preload-- or what happens at the end of diastole, which we call "preload"-- is going to have a huge effect on the left ventricle pressure during systole.