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I'm gonna draw for you the heart And we're actually gonna do a little zooming in now, taking a look at exactly what happens, both in the wall of the heart but also going even further in. So, let's start with the heart heart wall. What were you to see if you were to zoom in? You'd see heart cells. And this is kind of a heart cell with some branches here. And you remember that heart cells, besides just having branches is very distinct looking. Sometimes it has one, but sometimes it has two nuclei. Now let's say we were to zoom in again. on this heart cell. What would we see if we kind of went further? Well, you know that there are lots and lots and lots of proteins inside these heart cells, and the ones that we've usually been concerning ourselves with are the actin and myosin and these are kind of the classic cell proteins that allow it to contract. So, it might look a little bit like this, right, with our actins kind of spaced out a little bit from each other. I'll label it as I go. This is an actin. And, in the middle of the actin. And in the middle of the actin, you've got myosin. Right? So you've got this purple myosin. And it looks maybe something like this, with the little myosin heads. coming off of it. And you've got some on both sides. And these myosins are going to be tethered to the wall. Right? This wall at the end, and I'll draw that tethering with green, kind of like that. And this is basically, this is titin. Titin is kind of what keeps the myosin from floating away. And you can think of it as "Well, what happens over time is that these myosins and actins are gonna start binding", right? They're gonna start binding, and we call these actin/myosin crossbridges, or you might hear different terms, but basically the two are interacting with each other. And what the myosin is gonna want to do, is it's gonna want to yank this way, right? It's gonna want to bind the actin like this. and yank it that way. In fact, all these little myosins are gonna kind of act the same way, they're gonna wanna yank the actin in the same direction. And in the same way, you've got pulling in the opposite way. You've got pulling towards the middle. basically. So if this were to work, what would happen? Well, at the edges, at the end here, we call these guys z disks. Z-discs. You might have heard the term 'z-line', because it looks like because it looks like a line under a microscope. But if you actually zoom in, and you go up close to it, it's basically a disc of protein. Right? So these z-discs, if our actins and myosins and indeed interacting and tugging on one another, the way that we think that they should these are going to be pulled inward. It's almost like kind of bringing a wall in towards the center. You can kind of think of it that way. You can kind of think of the actin as a rope hanging off the end of this z-disc. And the myosin is literally got it's hands on it, yanking on the rope and tugging on the z-disc. In fact, lots and lots of myosin are doing it all at once. Kind of in unison. So that's why these discs get moved toward the center. And when they get moved toward the center, we literally call that 'contraction' of the cell. Or cell contraction. And so these actin ropes uh, if you want to keep thinking of it in that way, aren't going to be cut or shrunk or anything. They're going to stay the same length. But these z-discs seem to be brought closer together. the entire thing looks a litte bit more crowded, because the myosin has brought everything to the center. So that's cell contraction. Now, I'm gonna actually take a further zoom-in. Let's say you actually wanted to zoom in to something like this, this white box. Kind of take a look at what that might look like. Let's see that. I'm gonna make a little bit of space. Let's just keep that scene like that. Let me start my drawing the actin, it's gonna look something like this. And I'm gonna try to keep it somewhat consistent, and we're gonna see what it is that draw along the way. So we've got our actin and we've got our myocin. And our myosin, I'm gonna orient kind of in the same direction as our actin. It's gonna look something like this. Let's say it's one head there. And let's say we've got our second head there. So we've got our myosin. And of course our myosin is gonna continue in really in both directions, but the majority of the myosin is gonna be that way. So we've got our actin and we've got our myosin, and the story from the previous picture ends there, but we know that we've got our myosin actin binding sites are gonna be kind abound up by trophomyosin. Trophomyosin is gonna be snaking its through. Looks a little bit like that. And it's basically gonna be sitting in all binding sites that myosin really can't get in there. And in fact, there's also another protein. We talked about the fact that there's another protein called troponin. And troponin is also kind of in the same area I'm actually gonna draw troponin like this. You might be thinking "Why am I drawing troponin in three parts? Why is there a little crescent shaped thing and two little circles?" And actually, troponin, even though previously we've talked about troponin as one protien, this whole thing. It's probably more commonly known as 'troponin complex', instead of just the one word 'troponin'. It's actually a complex of proteins. And there are three to be precise. There's troponin-C over here. I, and T right over here. And if that's not clear, let me put it over on the side here. So there's Troponin-C, troponin-I, and troponin-T. And in yellow we've got our tropomyosin. So now our picture is looking a little bit more accurate, right? Now we've got all of this stuff going on, with the tropomyosin getting in the way of our myosin head. Now, what's gonna make that troponin complex move away? What's gonna kind of clear space for our myosin head? Well, we know that it's gonna be calcium. And I'm gonna draw calcium here, binding to which part of the troponin complex? Troponin c! C, like calcium. Is what's gonna bind the calcium. So troponin c is gonna bind the calcium. And once it does, once the calcium is down there, it now can scooch the tropomyosin out of the way. So, now the tropomyosin (I'm gonna draw this in green arrows), is basically schooched out of the way, and the myosin head is very happy. 'Cuz it can bind finally to the actin. Now, if there's no calcium. Like you can see in our friend to the right, this troponin is not gonna bind to the calcium. So the tropomyosin is not moved out of the way, it's in the way. And at the end of the day, the myosin is gonna be sad! Because it cannot bind to that actin. So you can see now, from a myosin standpoint, it likes when calcium is around. Because that means it can do work. Now let me clear a little more space for us, and I'm gonna bring up one final point. I mean, if we think that a happy myosin head is a working myosin head, if we take that approach, it's a little bit like I guess getting a job! Right, it makes everyone happy when they get a job. when they're employed. And myosin heads are no different, they want to be employed. So how do you employ myosin heads? How do you get more jobs for myosin heads? Well, there are basically two strategies for increasing what we call 'inotropine', basically getting more myosin heads working. So two strategies, let's go through them one by one. So the first strategy would be what? Well, you could affect the amount of calcium. You could get more calcium around. That would be one strategy. And the other strategy might be: you could have the troponin c Remember, the troponin c is part of the complex that's binding the calcium, You could get troponin c to be more sensitive to calcium. And I'm gonna put that in quotes. What do I mean by 'sensitive'? Essentially, you're saying that troponin c could change its shape or its confirmation to bind the calcium that's already around more easily. Basically, you're binding calcium more easily. But I wanted to put the word 'sensitive' because sometimes you'll see that word, and you'll wonder what it means. So bind calcium more easily. So these are the two basic strategies. And you could imagine increasing in one strategy, increasing the calcium, b but leaving the sensitivity of troponin c the same. Really, not changing how easily it will bind calcium. And the overall effect is more myosin heads are working! So more myosin heads are working. That would the overall effect. And you could flip it around. You could say Maybe you have the same amount of calcium, maybe you don't actually increase the calcium, but you do make troponin c bind the calcium that is there more readily. Or more easily. Well, in that siutation, you also get more myosin heads working. So in either scenario, in either strategy, you're going to get more myosin heads working. And so these are the two basic strategies for inotropy.