The Science of Everything Podcast - Episode 132: The Muscular System

Episode Date: November 9, 2022

A journey through the mechanisms of muscles and muscular contraction. I begin by outlining the key structural elements of muscle cells, including the sarcolemma, sarcoplasmic reticulum, the myofibrils and their myofilaments. I then explain the sliding filament mechanism of muscle contraction, and how it is governed by neural signals through the release of calcium. I conclude with a brief overview of the types of muscle contractions, the difference between fast twitch and slow twitch muscle fibres, and a short discussion of some metabolic aspects of muscle function, including the role of creatine phosphate. Recommended pre-listening is Episode 26: Human Organ Systems. If you enjoyed the podcast please consider supporting the show by making a PayPal donation or becoming a Patreon supporter. https://www.patreon.com/jamesfodor https://www.paypal.me/ScienceofEverything

you're listening to The Science of Everything podcast, episode 132, the muscular system. I'm your host, James Fodall. In this episode, we're going to take a tour of the muscular system, focusing on the structure and function of skeletal muscles. In particular, we're going to talk about the contraction and relaxation cycle that's at the heart of how muscles move, and the sliding filament mechanism, which is the molecular basis for muscle contraction. We'll also talk about some other aspects of muscle.

control, such as the control of muscle tension by the nervous system, different types of contractions, and some aspects of muscles and exercise. Recommended pre-listening is episode 26, human organ systems. Without further ado, therefore, let us begin. At the outset, I want to emphasize that although we're going to be talking about the muscular system generally, most of my remarks will be focused on describing the structure and function of individual skeletal muscles. What we won't be doing is going through a detailed gross anatomy of the muscular system. There are around 650 skeletal muscles in in typical human body. Most of our muscles form a bilateral pair, so there's one on each side of the body,

so there's about 320 pairs of muscles. And you can go through elaborate atlases, showing the different muscles in different regions of the body and going through all of their complex Latin names. We're not going to do that here because, A, it's only an audio podcast, and that doesn't work very well in this format. And B, I just personally don't think it's very interesting. So instead we're going to focus on the physiology, the structure and function,

and particularly how muscles work, how they move and allow us to manipulate the world. So the muscular system, as I said, it consists of about 650 different muscles, skeletal muscles, that is, and there are three different types of muscles in the organ system. So I already mentioned skeletal muscles. There's also smooth and cardiac muscles. So cardiac muscles we've actually already talked about in episode 122 when we talked about the respiratory and circulatory systems.

So I'm not going to go into any more detail about that here. You can refer to that previous episode. I'm also not going to say too much on smooth muscles because they're similar in many ways to skeletal muscles, although there are some differences. I'm going to focus mostly on skeletal muscles. So skeletal muscles are muscles that are connected to skeletons and they are under conscious control. So they're muscles we typically think about as muscles, right? They have a striated appearance. We'll talk a bit more about that later.

And we are able to control them using the somatic nervous system. So this means that we are able to voluntarily trigger muscle contraction and move around. So these are muscles in our arms and legs and torso and so forth, right? A muscle consists of the actual muscle tissue per se, the contractile part of the muscle, that does the contracting and relaxing. and in addition, some non-contractile tissue, which consists of dense, fibrous connective tissue that makes up the tendon that connects the muscle to the bone. So tendons attach muscles to bones, allowing us to move essentially our skeleton around. So that's why we call them skeletal muscles, because they're attached to skeletons.

They're under voluntary control, and they're responsible for essentially all voluntary movement, or most voluntary movement. So that's the overview of the muscular system. Let's now talk about the structure of a single skeletal muscle. So to introduce this, let's first talk about the fact that skeletal muscles are highly structured. So there's a number of different structural components and levels of organization. And it's a little bit hard to keep them straight in your head, especially when we don't have a visual aid to help us. So in order to keep ourselves kind of oriented here about what we're talking about and how the structure of the muscles fits together,

let me introduce the four kind of major structural levels at the outset, and then we'll go through and talk about them in a bit more detail. At the highest level of organization, you have the muscle as a whole, which will be connected to a bone via a tendon. The muscle is comprised of dozens to up to maybe a few thousand facchicles. A facchicle is a bundle of individual muscle cells or fibres, each of which is essentially a single cell. Each muscle fiber has multiple long structural units called myofibrils, and each of those, in turn, is comprised of multiple long proteins, which are called filaments. So we've got four layers of structure here.

Facicles, fibres, fibrials, and filaments. Now, fibrials, they're generally called myofibrils, but I'm going to call them fibrials, so that we have a consistency, and so they all start with f. The other nice thing is that if you kind of name them this way, they're actually in alphabetical order, which is how you can remember what order they are in, right? So fascicles, first in the alphabet, they are the highest level of structure, and then below that are the fibres, that's a single muscle cell, and then below that are the fibrils, or myofibrils, and then below that again are the filaments, which are essentially long proteins. So that's down

at the kind of at the molecular level. Okay, so that's the kind of major levels of structure in a skeletal muscle. So now let's go through and talk about each of those in turn. So starting at the largest level of organization, we have the fascicle. The fasciacle is just a bundle of individual muscle cells or fibers that are surrounded by a single layer of perimisium connective tissue. So faschicle is basically just a bunch of muscle cells that are bound up together and kind of structurally located together. The simple way to think about this is that whenever you have a bunch of things in a biological context that are sort of structurally and functionally related, they're usually surrounded by a layer of connective tissue. So there's a layer of connective tissue that surrounds a

fascial, and then there's another layer that surrounds the muscle as a whole. Now, as I said, each fascicle has many muscle fibers in it, and a muscle fiber, or just fiber, as we sometimes call them, is a single cell. Now, this is a little bit confusing, because muscle fibers, although they're an individual cell, so they're surrounded by a single plasma membrane, they have multiple nuclei, so they're multi-nucleate cells, and essentially they form out of many parent cells kind of fusing together during the development. process, but we're not going to get into that here. Because of this, they're very long cells, but it's still a single cell because it's still surrounded by a single plasma membrane,

and the internal cytoplasma is all internally connected to each other, so you don't have to cross an external membrane to get from sort of one part of it to another. So muscle cells are quite unique in that respect, as they're extremely long and have many, many nuclei in each individual cell. So because there are multiple muscle fibers in a fasciacle and multiple fasciacles in the whole muscle, an individual muscle can contain a very large number of muscle fibers. So, for example, the biceps in an adult male may contain around 250,000 muscle fibers. So there's quite a lot of duplication, if you like, at each level. Because of their unique structure and function, muscle cells have an associated set of special vocabulary to describe different aspects or structural components of the cell.

Cytoplasm of a muscle cell is called the sarcoplasm. So it's essentially just the same thing, regular cytoplasm, but it has its own special name, the sarcoplasm. The smooth endoplasmic reticulum, which if you haven't listened to the episode on the structure and function of the cell, the smooth endoplasmic reticulum is a folded membrane structure that exists inside all the eukaryotic cells, and it is a place where proteins are packaged up and folded and prepared for export to the rest of the cell. So it's an organelle within a cell. Now, the muscle cell, being a eukaryotic cell, of course, has a smooth endoplasmic reticulum, but it serves a special additional function in muscle cells, which we'll get to.

It helps with the controlling the process of contraction and relaxation. But the smooth endoplasmic reticulum in muscle cell is called the sarcoplasmic reticulum, and the cell membrane in a muscle cell is called the sarco lemma. So we didn't get too hung up on these words here, but just sort of for your reference, and if you encounter these terms elsewhere, this prefix here, sarco actually essentially just means muscle, but interestingly, the root effectively means cut, because of the, the sort of striated appearance of the muscles and is actually the same root as the word sarcasm, like a cutting remark, so I thought that was interesting. But anyway, so we've got our

psychoplasm for the cytoplasm, cycloplasm, for the smooth endoplasmic reticulum, and the sycalaema for the cell membrane. But these are kind of all the regular structural components of a cell. It's just that the muscle fibers or muscle cells have much many more of them than unusual because they're much larger and very long. And remember they're multi-nucleate. They also have the other regular components of cells like mitochondria and so forth as well. But there is something extremely important and unique about the sarcoplasmic reticulum because normally the endoplasmic reticulum of a cell will be localized to a part of the cell. You know, it's a fairly large organelle structure, but it doesn't dominate the whole cell, right? It's localized to a portion of it and

it's a system of connected membranes. But in a muscle fiber, it's rather different. The sarcoplacic reticulum is extremely large and perfuses through the interior of effectively the entire cell, and is therefore much larger and much longer and has many more connected components to it compared to a regular eukaryotic cell. So it's a very intricate elaborate network which extends throughout the entire length and breadth of the cell. And if you see a diagram of this, you'll see, well, that's a, the cycloplasiculum is just sort of goes everywhere, throughout the cell. And the other components like the mitochondria and nuclei, so forth, they just kind of squashed around the outsides or wherever they can fit in. Also throughout the muscle

fiber are, of course, the fibriles or the myofibrils, which are comprised of the filaments, which actually perform the contraction process, which we'll get to in a moment. But those are kind of the active units, if you like, that do the actual contraction, which is essential for the function of muscles. So they're all sort of stuck and spread out throughout the interior of the cell as well. In addition to its usual role in regular cells of serving kind of as a protein modification and distribution center, the psychoplasmic reticulum in muscle cells also serves the important role of regulating the transduction of electrical signals, or electrochemical signals, from innovating nerves that reach the muscle cell to all of the myofibrils, the organelles

that actually contain the contractile proteins that allow the muscle to change in size. the psychoplasmic reticulum is the network of tubes essentially that is able to transmit and disperse that signal throughout the individual muscle cell so that all of the fibrals can get the signal at basically the same time and contracted unison. It does that by releasing calcium, but we'll explain that a little bit more later. In order to enable the psychoplasmic reticulum to kind of reach all parts of the cell, there's a special structure called T-tubules, transverse tubules. And basically these are just extensions or protrusions of the sarcoplasmic reticulum, which allows neighboring kind of regions of the network to connect to each other.

We'll come back to the exact function of these later, but just bear in mind that these t-tubules essentially provide extra access of the sarcoplasmic reticular to all of the myofibrils located throughout the interior of the muscle cell. Okay, so that's a little bit about the anatomy and major components of muscle fiber. or muscle cell. Now let's go to the next level down again and talk about the myofibrils, or the fibral as I'm calling them, just to keep our levels clear. A myofibril is a very long, specialized organelle contained only in muscle cells, and their purpose is to contain the filaments, which are actually responsible for carrying out the contraction process. But the key thing

to bear in mind is that the myofibral is kind of a bunch of these filaments connected to and forming a single organelle. A muscle fiber, that is the muscle cell, contains a large number of these myofibril organelles, just like a eukaryotic cell contains a large number of, say, mitochondria, so to do muscle fibers contain a large number of these specialized myofibril organelles. So a single myofibyl contains a large number of the protein subunits, the two types of myofilaments. There are so-called thick and thin filaments. The thin ones are called actin, and the ones are called myosin. So these are words you may have heard of before, actin and myosin. We will come back to these again, but just bear in mind that within the muscle fiber,

there's a bunch of these myofibrils, and within each of those, there's a kind of a structure of these filaments, thick and thin filaments, which are held together by other protein structures as well, by parts of the cytoskeleton effectively. And they form a kind of an interconnected mesh network, but we will talk about that a bit more later. But it's these filaments that actually perform the contractive process that allow muscles to, well, contract. So before we jump right in and start to explain the actual mechanistic process of muscle contraction involving the myofilaments, let's just recap and take stock of the different layers of the structure of muscles to ensure that you sort of have everything in place and can see in your

mind how these different layers of structure fit together. Because again, the structure of skeletal muscles is quite confusing. So remember, we've got kind of four levels of organization. At the very outer level, there's fascicles, which are the bundles of fibers, a bundle of which together, surrounded by connective tissue, makes up the muscle itself. So within a single fasciacle, you've got a bunch of these muscle fibers, each of which is just a single muscle cell, although each cell is very long and has many nuclei within it. Each myofiber contains a large number of specialised, very long organelles called myofibrils, which are surrounded by a dense network of connected membrane-bound tubules called the sarcoplasmic reticulum, which is the special

muscle version of the endoplasmic reticulum. And within each myofibril in turn is a large number of these long protein units, which are called the myofilaments, or just the filaments. There's the thick filaments, which are myosin and the thin filaments, which are called actin. Okay, so now that we've set out the kind of basic idea of what the structure is and the major components, let's talk about the contraction and relaxation cycle and then move on to the sliding filament mechanism. The essential functional unit of a skeletal muscle is called the sarcomere, and it's a little bit hard to explain exactly what a sarcoma is without just kind of explaining how it works. So just bear that word in mind and we'll kind of go through the idea of how everything fits together here.

Also, there's quite a lot of terminology that goes into, describing sarcomeres and the contraction and relaxation cycle. I'm not going to use all of it here because a lot of it's quite confusing. So just for those of you who may have heard of this before, there's terms like the i-band, the a band, the m-line, the z-disc, the h-zone and so forth. And these terms initially come from microscopic analysis of muscle tissue and are not very descriptive because they're based on initially just sort of anatomical analysis of all, you know, there's this bit here and this other bit here and this bit that's darker and so forth. and as such it's useful from that point of view but it's not very useful for understanding what's happening

because the names are meaningless so i'm mostly not going to use those i'll try to describe it more descriptively and provide a picture without necessarily referring to all of these letters which again themselves don't have a lot of meaning so here's the basic idea of a structure of one of these myofibrils or these fibules of which there are many scattered throughout the interior of a single muscle cell. Now the key functional unit of a myofibral is called the sarcomere. And basically a myofibral just consists of a bunch of sarcomeres end to end in the sort of long sausage that forms the organelle in the muscle fiber. So let's talk about a sarcomir. Now sarcomeres are quite complex in their structure and they're rather hard to describe. So in order to describe what it kind of looks like

and the different pieces of it without using a visual aid, I'm going to use an analogy. So for this analogy, let's imagine three discs. You can imagine they're made of cardboard or whatever, right, but it's a round disc. And then what I'm going to do is I'm going to take two of these discs, and I'm going to blotack candle to them, like candles that you put on a birthday cake, like birthday candles. I'm going to blotack the candles to one side of two of these discs. So I've got basically two like birthday cakes, except there's no cake. It's just the, like, the cardboard disc, and then the candles blue tacked on top of them. And the candles are separated sort of fairly evenly over the top of the two discs. The candles are kind of long and relatively thin,

maybe longer and thinner than regular candles, but otherwise that's what we have. And then what I'm going to do with my third disc is remember I had three of these round discs. For the third one, I'm going to take another set of candles. So these are fatter candles, not like the thin ones that I had. These are kind of fat boys. And then I'm going to push them through. I'm going to make little sort of holes within the third disc that I have. I'm going to shove them through so that they're sticking out either side and kind of lodged them in place there. So this third disc, which is my middle piece, so this middle piece has thick candles that are wedged in, so they're poking out kind of halfway either side of the central. So now I've got three components.

I've got my two end pieces, so those are the ones where I've got the thin candles blue-tacked to one side of the disc, and then I've got my middle piece, which is the one with the thick candles poking out either side. And then what I'm going to do is I'm going to take these three pieces and set them up kind of like on edge so that the cardboard disc that serves as the base of my for my thin candles and also the thing that my thick candles are pushed through. I'm going to set those up so that they're sort of standing on their edge. So I'm going to have on the left hand side, I'm going to flip up now my cardboard disc with the blue tact to it. So I'm going to stand that on its edge and so the candles will now be facing to the right. So imagine looking from left to right.

you've got your cardboard disc and then the candles face to the right. And then in the center, I'm going to put my centrepiece so that the thick candles are facing out in either direction. And then finally, on the far right, I'm going to put my third piece, the end piece. I'm going to put that so that the thin candles on that are facing inwards towards the middle piece. So on either side of the middle piece, I've got my two discs with the thin candles and they're both facing inwards.

So I've got disc, thin candles facing inwards, and then I've got my middle piece with the disc and then the fat candles poking out of either side, and then on the far right, I've got my last disc with thick candles facing inwards again. So it goes thin candles, thick candles, and then thin candles again. Now, if I tried to set this up, it would sort of fall over, but what you have to imagine is there's this kind of just network of string and wires or whatever that kind of keeps it in place. We're not too worried about that for the moment. Now, this elaborate structure here of these three disks and the two different sets of candles of different thicknesses that are kind of pointing in towards each other is analogous to the sarcomere.

And the key thing to understand, which I have an emphasised at this point, is that the candles, the thick and the thin candles, they don't just face towards each other, they actually overlap. So there's some region where you just have thin candle, and then there's a region where you have thin and thick candle, kind of next to each other, but not touching, but they're near each other, and they're kind of parallel. And then there's a region right near the centre where there's only thick candle. And then likewise, that structure is duplicated on the other side as well. So if we go from left to right and sort of visualize moving across this whole Sarkomir model, we start. with the base on the left end, and then there's thin candle only, and then there's thick candle overlapping with thin candle, and then there's thick candle only, and then there's the middle base in the middle, and then on the other side, now to the right-hand side, there's a region where

there's thick candle only, and then there's thick candle overlapping with, or like parallel to the thin candle, and then there's a region with thin candle only, and then finally we have our circular base at the far right side. So that's the whole sort of sarcomere model. And hitherto, instead of calling these candles, because that was just for purposes of visualization, I'm going to call these rods. So we've got the thin rods on either end and the thick rods are going through the disc in the center. And these rods are analogous to the myofilaments, or just the filaments. So there's the thin filaments, the actin, and the thick filaments, the myosin, which we'll be talking about, and I'll explain more about the structure and function of these different types of filaments in a moment.

So that whole strange sort of unit that I've constructed there is analogous to the sarcomere. So the sarcomere consists of these kind of end units, which are called the eye bands, but we're not going to worry too much about that. Basically, there are structural proteins that hold the whole thing together, and those are kind of analogous to my round discs at either side and also at the center. Plus the thin and the thick filaments, which interdigitigitate so that they kind of interpenetrate each other like you, holding your fingers together towards each other, fitting in between the gaps in your fingers from the other hand. So this interdigitating structure of the thin and the fifth fibres is sort of critical and at the core of the structure of each sarcomere. And to kind of jump to the punchline before we go through the details, the way that a muscle contracts is by shortening. So I mean, that's what contraction means.

So when we want to, let's say, move our arm upward, we'll go through the different types of contractions and details a little bit more later. But just for purposes, now, imagine you're contracting your bicep and sort of, raising your lower arm towards your face, right? So what happens there is that your bicep contracts. And in doing so, it exerts a force on the tendon, which pulls your lower forearm towards your head. So the point there is that in order to perform a movement, what you need to do is contract a muscle. You need to make it shorter. As the muscle gets shorter, that exerts a force on the tendon, which exerts a force on the bone, which pulls the bone up, and that pulls your arm up. So that's essentially how all muscles work. There's a bit more to it, which will get to

a little bit later in this episode. But the basic idea is to move something the muscle needs to contract. It needs to get shorter. And that allows you to then exert forces on tendons and then on bones and so forth. So how do muscles get shorter? Well, the answer is they get shorter because each sarcomere within the myofibrils in each muscle fiber. The sarcomeres get shorter. So they actually shrink.

They don't shrink sort of width-wise, right? Because they're long and thin. They don't shrink width-wise, but they shrink length. So they get smaller lengthwise. So each sarcomere shrinks lengthwise, which means the whole myofibral shrinks lengthwise, which means the muscle fibers shrink lengthwise, which means the fascicles shrink lengthwise, which means the muscle itself shrinks lengthwise. The muscle kind of shrink throughout its length in many kind of microscopic increments, which leads to put together the whole muscle shrinking in size. Again, lengthwise, so contraction we call that. And so that's how

muscles work, they shrink in size or conversely relax, which elongates them, thereby exerting forces on tendons, which exerts force on bones and so forth. That's the basic idea. So it all comes down to a sarcomere contracting, getting thinner. And how does sarcomeres contract? Well, sarcomia's contract by, if we go back to my loose analogy of the circular end discs, right, which remember have the thin filaments attached to them, those. Those. two components move closer to the center. Remember that there's a disc at the center which has the thick filaments coming out either side, the myosin filaments. Well, these kind of, if you like stay in place, I mean, the whole muscle's moving, but you can imagine looking at from the point

of view of the center here where you've got the thick filaments coming at either side. Imagine that that's fixed in place. What happens is that the thin filaments move closer and the discs that support them. They move closer, both from the left side and to the right side. So they're pushing inwards from both sides. So therefore the whole sarcomere contracts because the left side moves closer to the center and the right side moves closer to the center. And the way that that can work is because, remember I said that the thin and the thick filaments, they overlap. They're like interdigiting. So there's some degree of overlap, but not complete overlapping, right? What happens is that as the sarcomere contracts, as the muscle contracts, the overlap between them increases.

So there's less of a distance between the end disks on either side of the sarcomere and the point where the thick filaments end. So instead of the thick filament extending like halfway towards the discs on either side, it will extend, when the muscle fully contracts, it will extend nearly all the way. And conversely, when the muscle relaxes, instead of, say, the thick filament extending halfway towards the end disc either side of the sarcomere, it will extend. end only maybe a third of the way, and there'll be very little overlap between the thick and the thin myofilaments. So to recap, muscles contract by sarcomeres shrinking in length, and therefore the whole

muscle shrinks in length. The way that a sarcomere shrinks in length, or contracts, is by the thin and thick myofilaments overlapping more, which brings the end discs, as I'm calling them, which support the thin filaments, which brings them closer to the central disk. As the end disk get closer to the central disc, the overlap between thick and thin filaments increases, and the length of the sarcomere is decreased, so it contracts, it gets smaller. The converse happens when the muscle relaxes, the thin and the thick filaments overlap less, the end disks move further apart, and therefore the sarcomia increases in length, and therefore the myofibrils increase in length, the muscle fibres increasing length,

the fascicle's increasing in length, the muscle increases in length, right? So it kind of goes up the chain. So that's the basic idea of how muscles contract and the role of the sarcomia in that. So what we're going to discuss now is the mechanisms for that. So I've just sort of said that this happens, right, that there's a change in the amount of overlap between the thick and the thin filaments. But I haven't explained how that happens and also how that's governed by the nerves. I mentioned before that skeletal muscles are controlled by impulses in the somatic nervous system. But I haven't explained how that actually works, how that connects to these filaments. So that's the next stage that we're now moving towards.

And specifically, we're going to talk about the sliding filament mechanism. So this is sort of the standard model, standard way of understanding how it is that the thin and the thick filaments interact with each other as well as with the innovating nerves and other components, which we'll get to, in order to actually produce contraction of the sarcomere. So in order to understand the sliding filament mechanism, we need to explain a little bit more about the actual detailed structure of the thin and the thick filaments. Because so far I've just called them the thin and the thick filaments and I've given them names, but I haven't really said much about them and their specific structure. And we're going to need a little bit of that to make progress

here with the sliding filament mechanism. Okay, so let's start with the thin filaments. I've mentioned a number of times that the thin filaments are the actin filaments made of subunits, multiple subunits connected together of a protein called actin. Now, this is a bit of an oversimplification because actually the thin filaments consist not only of these acting units which are connected together and kind of wind together in two interconnected kind of helices. But in addition, there's two other component proteins that make up the thin filaments. So in addition to actin, there's also a protein called troponin and another one called tropomycin. Now this is very confusing because tropomycin has a very similar name to myacin, which is the main protein units that make up

the thick filament. So henceforth, I'm not really going to talk about tropomycin because I don't want it to get more confusing that it already is. So I'm mostly just going to talk about thick and thin filaments, and actin will sort of be the representative name of the thin filament. But bear in mind that there's actually these two other components as well, propamycin and troponin. And I'll talk more about troponin in a minute. They have important roles, but it's just the names are a bit confusing. So that's the actin filament. There's sort of these three components with confusing names. Then there's the myosin or the thick filament. Now, the thick filament is comprised of many myosin molecules which are kind of joined up or

connected together. But the important thing is that a mycine molecule consists of essentially a long shaft region and then what's called a head or mycine head. And probably the easiest way to explain what this looks like is to imagine an ear cleaner with that bit that sort of swells and protrudes out, right, that you stick in your ear. Except just imagine kind of bending that a little bit. So it's kind of a straight shaft and then this sort of swelling bit at the end that it's kind of a bit bent relative to the shaft. That's kind of what the mycine filament looks like. And the myison filaments in the, as part of the thick filament, are kind of resting parallel to the actin filament, right? So they kind of sit alongside each other, such that the myosin heads are kind of point or bent

bent partway towards the actin filament. So you've kind of got these two long filaments next to each other, but then there's these kind of bent swelling heads of the myocin, which bend up towards the thin filament. So these myosin heads are kind of core to the sliding filament mechanism. They are kind of doing the work of actually moving the filaments with respect to each other. So the way it works is like this. These actin proteins that form the actin filament on the thin filament, these have special binding sites for that myocin head, right? So they're sites in the protein where the myocin can actually bind

and form a bridge, a connection between the thick and the thin filament. So this is called a cross bridge. This is a form of an intermolecular bond between the thin and the thick filaments. When that cross bridge or when this bond is formed, that triggers a conformational change in the myosin head, which causes it to essentially bend backwards. So remember, you've got this kind of like ear cleaner structure with the thin shaft and then the head that kind of bends up somewhat towards the thin filament. Well, when this crossbridge form, so when the myocin head finds this binding side on the thin actin filament, that causes it to bend backwards. So instead of just bending like the head bending partway towards the thin filament, it actually bends all the way around backwards, like more than a 90 degree bend.

And what that does is that is what. actually pulls the thin and the thick filaments relative to each other. Specifically, it pulls the thin filaments towards the center. Remember my central disc with the thick rods sticking out either side. This bending backwards, a conformational change of the myocene head actually pulls the thin filaments and the end discs that they're connected to. It pulls them towards the center of the whole sarcomere, thereby slightly shrinking it. Of course, a single myocin head is not really going to do very much. but many, many of them in combination, bending back in this way, causes this shrinkage. So if you're wondering, what is literally the specific physical change that produces the shrinking

or the contraction of the sarcomia? It's this bending backwards, this conformational change of the myocin heads following the cross-bridge formation, the binding between the thick and the thin filaments. That's what actually produces the contraction. Of course, there's many steps needed to actually get that to happen and then to have it controlled properly and so forth. but that's the action that most directly causes the shrinkage of length of the sarcomia. This process of forming the crossbridge and then the myocene head bending backwards consumes energy in the form of ATP. So once this binding and the bending backwards has occurred, the ATP molecule is spent and so disassociates in the form of ADP and inorganic phosphate. So those are the two kind of components.

Hopefully you may recall if you've listened to previous episodes that ATP is essentially like an energy carrier molecule, stands for adenosine trifosate, so it's essentially a molecule with three phosphate groups attached to it. These phosphate groups are very high energy, and so when we kind of break one of those off to turn it into ADP, adenosine diphosphate, it's kind of lost energy. And so you can imagine each of these phosphates is kind of like on a spring, and then when we release one of those springs, the phosphate is removed, and we release energy. So this process of the bending back, of the forming of the bridge, and then the bending backwards of the myosin heads, this consumes energy in the form of ATP. So once the bending backwards and the moving inwards of the filaments has occurred, the ADP and inorganic phosphate dissociates, and that opens up a site for a new ATP to bind.

So basically the used up energy products, if you like, a dissociate, and a new energy-rich ATP molecule binds on. And that binding of the new ATP molecule causes the mycine head to detach from the actin thin filament and return to its resting position. So remember when it bends back, it kind of has more than a 90 degree bend. Well, it returns back to its, say, like a 45 degree resting position, ready to then bind again to the actin filament when it finds a new binding site. So this whole process of myocin head finding a binding site,

forming a crossbridge, bending backwards, using up an ATP in the process, ADP and phosphate then dissociate, allowing a new ATP energy-rich molecule to bind, which then causes the myocin head to detach and return to its, initial position which then allows it to find a new binding site which then causes it to bend back again which then uses up the ATP into ADP and phosphate which dissociate allowing a new ATP to bind which then causes the mycine head to return to its resting position

and so on and so forth this whole process is called a power stroke so each of these is sort of like the power stroke of an engine right in that it's it's sort of one turn of the dial if you like each time it does this the thin and the thick filaments are pulled relative to each other or specifically the thin filaments are pulled slightly inwards towards the central disc of the sarcomere. Each individual power stroke doesn't do that much, but many of them with many myosin heads and then many of these filaments in many muscle fibers, in many facicles and so forth, all of them together combined to produce a very large force. And that's the basic operation of how a sarcomia actually contracts. Now there's an important component that I haven't explained yet, which is how

the whole process is regulated because so far in explaining the power stroke mechanism it would might seem like that muscles would just always be contracting right because i haven't explained how the process is turned on and off right obviously we don't want the myos and heads always to be binding and then bending backwards because then muscles would always be contracting and then we'd never be able to relax them we'd just constantly be in a state of maximum muscle tension which is called tetanus and that would not be good so in addition to the mechanism for actually contracting we need a mechanism to turn this off so that we only contract the muscles when we need to, right? And they're not always being contracted. A muscle that always contracts isn't that useful.

This is now what we're going to explain, how we actually control muscle tension and how we turn on and off process of muscle contraction. And this is where the nervous system comes in. This is also where the sarcoplasmic reticulum comes in, which I mentioned before, as well as the T-tubules, and the troponin component of the thin filament, which I also mentioned. These all make their entrance now when we explain how it is that we control the process of muscle contraction. So to understand how we control the process of muscle contraction, we need to start at the top, so to speak. That is with the nervous system, because ultimately, skeletal muscles are under conscious control, as I mentioned before, and therefore they're under the control of the nervous system. And because skeletal muscles are controlled by the nervous system, ultimately the series of neural impulses that are sent down the nerves begins at the brain,

or the central nervous system somewhere. and then there'll be a series of action potentials, which are propagated across neurons, and eventually those will terminate at the axon terminal of a neuron that directly innovates a muscle cell. So for more information on how that process works of action potentials and transmission of neural impulses across different synapses in the nervous system,

have a listen to episode 38 neurons and synapses. But here I'm not going to really discuss that in too much detail because we're interested in the muscular system. So just suffice it to say that there's a series of neural impulses which terminate at the axon terminal, so the end essentially of the axon of a motor neuron that synapses with the muscle. And when the action potential reaches the terminal of that axon, that leads to the release of a neurotransmitter called acetylcholine. So astatylcholine is contained in these vesicles, so membrane-bound spheres essentially

in the terminal regions of the motor neuron. and in response to a change in the membrane voltage, which occurs when the action potential reaches the end of the neuron, the acetylcholine-containing vesicles bind to the membrane and then dump out their cargo of acetal-colon neurotransmitters into what's called the synaptic cleft, which is just the gap between the presynaptic motor neuron and the membrane of the recipient muscle cell. On the membrane of the muscle cell, there are located acetal coline receptors. So these receptors are protein structures which are sort of sensitive or waiting for acetylcholine to bind into them in particular binding sites. When that happens, the receptors trigger a

confirmation change, which then depolarizes the membrane potential of the muscle cell. So effectively that means it changes the membrane potential in the muscle cell and triggers an action potential in the muscle cell itself. So an action potential is basically a self-propagating change in local membrane potential, so electrochemical potential basically it means there's a change in the kind of concentration of ionic charge on one side of the membrane relative to another. Again, for more details, see episode 38 on that. But this action potential then propagates along the membrane of the muscle cell. Now, so far, this is all kind of fairly standard stuff in terms of how neural signals are transmitted

from one neuron to another across the synaptic left, using. neurotransmitters. One difference here is that the neurotransmitter is acetylcholine, which is different from neurotransmitters that are often used in other contexts. But the other thing that's different here is the structure of the plasma membrane. Remember that the plasma membrane of a muscle cell is called the sarco lemma, because it has a special structure that's different to ordinary cell membranes. For one thing, it is much larger because remember a muscle cell or muscle fiber is very long and much larger than ordinary cells in the body. But the other thing is that it has, has all these sort of internal folds and tunnels within it, which increases sort of the surface

area of the external membrane. I mentioned before the structures called T-tubules, which are kind of these tunnels in the membrane that connect one side of the cell to the other side of the cell, it crosses lengthwise direction. So that, you can imagine if you had a sausage and you, like, poked a toothpick from one side to the other, and then you poked a lot of those along the length of the sausage. That's kind of what the T-tubules are like. So the sarco lemma or the plasma membrane surrounds the outside of the sausage,

but it also kind of pokes through it and goes from one region along the long side to another. And the reason for that is basically to provide more surface area for the action potential to propagate along and enables the action potential of the change in the voltage to spread across the internal parts of the cell more rapidly. And we'll see why that's important in a moment. So basically at this point we have action potentials being generated as a result of the opening of these receptors or the channels connected to the receptors. You then have that action potential propagating along the sarco lemma, the plasma membrane of the muscle cell, including along around the outside surface and also through these t-tubules, which gets it access to the sort of internal space within the very long muscle cell. The action potential propagating across the sarco lemma and including in the t-tubules then interacts with the sarco-plabiales, then interact with the sarco-plabial. reticulum. Remember, that's the special version of the endoplasmic reticulum that muscle fibers have.

And unlike the regular endoplasmic reticulum in regular cells, which just sort of occupies its own part of the cell, the psychoplasmic reticulum is spread throughout the entire cell. It's a dense network of interconnected tubes and sacks, which is spread throughout pretty much the entire internal region of the cell. and the sarco lemma, the plasma membrane of the cell as a whole, plus the T-tubules, essentially wrap around key parts of the psychoplasmic reticulum. So basically, the psychoplasmic reticulum always has ready access to the cell membrane, because otherwise if you didn't have these T-tubules, the problem would be that parts of the sarco-lema that were close to the sarco-plasmic reticulum, like around the edges of the cell, would easily be able to propagate information

about the action potential to the sarco-placric continuum. But the parts in the middle of the cell that are a long way from the outside of the cell would take a lot longer for that signal to reach there. And so it would be difficult to synchronize different parts of the cell. Remember, a single muscle cell is comprised of a large number of elongated units called the myofibrils. So these are essentially organelles that are the contained the myofilaments that we just talked about. So each of these myofibrils, essentially you want to have them synchronized with each other so that they're contracting at about the same time. But you can't do that if you are relying on a signal to be transmitted slowly from the outside of the cell to the middle parts of the cell,

because that takes time, and then you'll have the issue where myofibrils near the edge of the cell contract first, and then myofibrils near the center of the cell contract later, and you don't want that. So that's why we have these t-tubules, which allow sort of ready axis of the membrane from the outside to the inside parts of the cell, thereby ensuring that myofibrils spread throughout the cell can contract around a similar time. So we have the action potential spreading across the sarco lemma, across the t-tubules, and then kind of interacting with the different parts of the sarcoplasmic reticulum, which is spread across the inside of the cell. But I haven't said yet what the sarcoplasmic reticulum actually does.

I've said it's important for ensuring that the myofibrils and their corresponding sarcomeres contract around the same time, but how does that actually work? Well, the key insight here is that the psychoplasmic reticulum contains excess calcium ions. These calcium ions normally kind of just live or are stored in the psychoplasmic reticulum, which remember is spread throughout the whole cell. However, when there is a change in the membrane potential, so when there's an action potential that sort of comes along, this triggers a release of calcium from the psychoplasmic reticulum into the cytosol.

So now we have an increase in the concentration, of calcium ions in the cytosol relative to previously. Calcium then diffuses throughout the cytosol, which brings it into contact with all of these myofibrils, or the fibrials, which I remember the long-contractive units that contain the filaments. When the calcium comes into contact with the filaments, specifically when it comes into contact with the thin filaments,

what happens is that the calcium binds to a particular site on the thin filaments. And it's actually this special protein called troponium. which is located, which is sort of bound to the surface, if you like, of the thin filaments. I've talked about the thin filaments before is primarily comprised of actin. That's kind of like the key structural element. But I did mention that there's actually two other proteins in there as well. Troponin was one of those.

And so troponin is this protein which binds to calcium, but it's connected to the actin units along that make up the structure of the thin filament itself. So we don't need to worry too much about the fact that it's a separate protein that the important part is that the calcium ions that have released from the sarcoplasma particulum diffuse through the cytosol come into contact with the thin filaments and bind to specific binding sites on those thin filaments. What does that do? Well, what happens when calcium binds to the thin filaments is that the third protein that makes up the thin filaments, tropomycin, that's the one with a confusing name, because it sounds like the mycin from the thick

filaments, but don't get confused. This is tropomyosin, one of the component proteins of the thin filaments. Tropomycin normally blocks the binding sites where the mycine head binds to the thin filament. Normally it blocks those, but when calcium binds to pronin, tropomycin changes confirmation. Essentially, it moves out of the way, revealing those myosin binding sites, and thereby allowing the mycine head of the thick filaments to bind to those binding sites, thereby initiating a power stroke. So the presence of calcium is what activates this power stroke cycle, which progressively contracts and then relaxes the sarcomeres and therefore the muscle as a whole. In the absence of

calcium, tropomycin returns to its initial confirmation, blocking the myosin binding sites, and thereby preventing this power stroke cycle from occurring. So only when calcium is present is the power stroke cycle able to occur. When is calcium present? Well, calcium is present when it's released from the psychoplasmic reticulum, and it's released from the sarcoplasmic reticulum in response to an incoming action potential that's sort of delivered throughout the cell by the sarcolemma, the plasma membrane, as well as the t-tubules, which spread the action potential throughout the cell. And this is what ensures that different parts of the cell have similar concentrations of calcium ions at a similar time, which therefore also ensures that they

contract at a similar time. Again, otherwise you would have different myofibrils, the different organelles in different parts of the cell, they would contract at different times, which would then lead to them some contracting while others are relaxing, and then you wouldn't have a coordinated generation of force, so that's not desirable. So that's why you need this intricate network of the T-tubules, plus the psychoplasmic reticulum spreading across the whole cell. Because the cycloplasmic particular has to be in contact with most of the surface area of the myofibrils in order to ensure that they get the calcium ions quickly and spread across the surface sufficiently so that they unblock the binding sites for the myocin quickly and then block them again also quickly

when the time is right. So you need this for the coordination to happen. You might be wondering, well, once you release calcium from the psychoplasmic reticulum and once it binds to the binding sites, what happens to it? Like, doesn't it just sort of stay there and then the contraction cycle keeps going? Well, no. Actually, what happens after a certain period of time is that the calciums are pumped out of the cytosol back into the psychoplasmic reticulum. So there's, there are pumps, basically protein complexes that pump these calcium ions back into the psychoplasma particulum and maintain a equilibrium concentration there. That equilibrium is disrupted when there's an action potential that leads to the release of calcium ions, but that's transitory. It doesn't last

for very long. In a short fraction of a second, the calcium ions will be pumped back into the cycloplasm of particulum, restoring the initial equilibrium, and thereby removing the calcium from the myosin binding sites, and thereby leading to the sites for the myosin to be blocked once again, and so thereby preventing further contraction. So this whole process means that each time the muscle cell receives an action potential from the motor neuron, the neuron that connects to it, it will trigger this contraction response. And a single instance of this sort of contraction response occurring in response to a single action potential on a motor neuron. This is called a twitch, not the streaming website, but just the idea of a muscle twitch. A single muscle twitch has a contraction phase that lasts

about 20 milliseconds. And each power stroke, according to a paper that I looked at, lasts around one millisecond. So that means each time you have an action potential that is detected by a muscle fiber, it will initiate a muscle twitch, which will be comprised of maybe something like 20 power strokes. So that's, remember, each power stroke is one instance of the myosin head, binding, bending back, and then dissociating, and then bending back, and then binding again. So it's sort of like 20 pushes or rows of the oars, if you like, each time you receive one action potential from a connected motor neuron. Now, it should be borne in mind that a single muscle phymer, muscle cell, is likely not going to be connected just to a single motor neuron. There may be multiple

motor neurons that innovate the same muscle cell. And of course, each motor neuron may be connected to it in multiple locations. So it's not just like it's one axon terminal and one connection with a single muscle cell. It could be multiple connections with multiple different motor neurons and so they could activate it more than just sort of one twitch at a time and then this is how we then control the strength of muscle contraction or what's called muscle tension so the more rapidly we want to contract the muscle so the more force we need the more impulses are sent to the neurons that to the motor neurons that innovate that muscle and this results in multiple twitches which overlap both kind of in space and time right so basically you can have an instance where

one neuromuscular junction initiates one twitch of the muscle, but then before that one is finished, another neuromuscular junction in the same muscle fibre, but located at a slightly different location, that one then initiates a twitch, and then another one initiates a twitch, and so these sort of sum over time. And essentially, the more rapidly and the more of these signals are sent, the more the muscle contracts. There is, however, an upper limit to this, when the muscle is sort of contracting as much as rapidly as it possibly can. Basically, you can think, of this as all of the calcium has been dumped out of the psychoplasmic reticulum, and it's not being pumped back in, or at least the rate of which is being pumped back in is equal to the rate

it which has been released. And so you're sort of having maximum power strokes just continually. So that's the maximum amount or the maximum rate at which a muscle could contract, when all the calcium's out and all of the filaments are just executing continual power strokes. That's as much as you can get. That results from a sort of a maximal summation of these individual switches and is called complete tetanus of a muscle. So that's when you have maximum muscle tension and the highest amount of force being generated by the muscle. There is another related term here, which I want to mention, that of a motor unit. So a motor unit is a single motor neuron and the fibers that it innovates. So I mentioned the fact that a single muscle fiber can connect with or synapse with a

single muscle multiple times. So it's not just like it's connected once, but it actually can have multiple connections. But it's actually a bit more complicated in that because a single motor neuron can actually innovate multiple different muscle fibers. On average, it's about 150 or so. So you have one neuron that connects to multiple muscle fibers. Usually the muscle fibers are dispersed throughout the muscle rather than like clustered into one region. So you can think of one neuron that's connected to lots of different fibers that are spread throughout the muscle. And then of course there'll be another neuron that connects to a different set of like 100 muscle fibers and so forth. smaller the motor unit, the more precise motor control is possible. So essentially, the fewer muscle

fibers I have innovated by a given motor neuron, the more precise I can be about exactly how I control my muscle. And we tend to find that with like fingers and other regions of the body where precise control is most required. The motor units are relatively small. So we have more precise control, more neurons for each muscle, whereas in regions like the buttocks, for example, where precise control is not as necessary, you have many more muscle fibers for a given number of input neurons. Now, there's different types of contractions that a muscle can perform in addition to sort of how strong the contractions or how rapidly the contractions are being performed. So that's the difference between like a single twitch versus summing multiple twitches and then complete tetanus at the extreme level. In addition to that, there's different types of contractions which depend on how the length of the muscle is affected relative to the amount of contraction that's performed.

So there's three main types that we identify here. Concentric contraction, eccentric contraction, and isometric contraction. contraction. So probably the simplest to understand is concentric contraction, and that occurs when the muscle contracts and it reduces in length. Now you might be wondering, well, isn't that the whole point of a muscle? I've just been explaining at great length how the sarcomia shrinks in length, and that shrinks the length of the whole muscle, which then pulls on the tendon, which pulls on the bone, muscle reduces in length, exerting a force on the bone, which causes the bone to move, right? Like, isn't that the whole point of a skeletal muscle to contract in length? Well, in a sense, yes, but that doesn't always happen.

because it depends on what opposing forces are also applied to the limb in question. So let's imagine again the lower forearm. So when you contract your muscle and bring that up your lower forearm up towards your face, that would be an example of a concentric contraction. The muscle is contracting and it's also reducing in length there by pulling your lower forearm towards you. But the opposite can happen. If I was to place a strong force, say on my hand, that pushes downwards at the same time as I'm contracting my bicep and then pulling upwards, if the downward force actually exceeds the upward force, then my forearm can actually sort of bend away from me and fall down, and that would result in an eccentric contraction.

So an example of this is if someone gives me a heavy object, and I contract my muscles to try to hold it, but the object is still too heavy, and my hands sort of bend downwards away from me, because I'm struggling to hold it, right? That would be an eccentric contraction. And basically what that means is that the muscle is contracted, and pulling, but it doesn't generate enough force to kind of pull backwards, and so it goes in the other direction. So essentially, an eccentric contraction results from when there's another force that is exceeding the force that the muscle is generating. And so in that case, actually, the muscle is doing negative work on the bone or the limb in question. Negative work because it's moving in the opposite

direction to that in which the force is being applied. Now, the compromise case, or the halfway case, called an isometric contraction is when the muscle is contracting, but there's no net movement in the bone that is connected to or the limb, whatever it is that's being moved. So an example of that is if you're just holding a heavy object. If you're holding it steady in place, you're exerting a force on it, but also gravity, say, is exerting a force on it in the opposite direction.

The force is cancel, and so it doesn't move. So there's no net motion, so you're not doing work on the heavy object, but you are still using energy. That's often something that people get confused. is that you only do work on something if you're moving it, but that doesn't mean you're not exerting energy or exerting a force on it. It just means you're not exerting a net force on it, which results in motion.

So if you're holding up a heavy object, you're exerting a force on it, but you're not doing work on the object. And that's called isometric contraction, where the muscle contracts but stays the same length, because there's an opposing force that is acting in exact opposition to the force that you're applying to the object. Now, another important distinction that we need to make

is that between two major types of skeletal muscles. So called type 1 and type 2. But I'm not going to use those terms because they're meaningless. Instead, I'm going to refer to them as slow twitch and fast twitch. So type 1 is slow and type 2 is fast, but again, don't worry too much about that. So the difference is in terms of essentially what type of force or load they're optimized for. So fast twitch fibers are most useful for rapid, powerful contractions. So they can sustain very high.

high forces, but for relatively short periods of time. So think like weightlifting or sprinting or something like that. Slow twitch muscle fibers by contrast sustain long contractions over long periods of time, but the total force that they generate is lower. So these are for things like long distance exercise or just things like standing, like maintaining posture. Those muscles have to be active for long periods of time, but they don't need as larger force. Because of the functional difference between them, there's also many structural differences that support that. So slow twitch fibers tend to be smaller and have a higher density of mitochondria. The high density of mitochondria is useful because they require a steadier supply of energy. And so they make greater use of oxidative phosphorylation,

which is another difference. If you recall, we've talked about this before, that there's sort of different stages in the metabolism of glucose. The first stage is glycolysis, and then the second stage after that is oxidative phosphorylation, which extracts extra energy from them, but that requires oxygen. So slow twitch fibers make at least greater use of that and thereby are able to produce a very steady supply of energy over long periods of time. The cost of that is that you need more mitochondria and greater blood supply for more oxygen. Whereas the fast switch fibers, because you need the energy really quickly and you don't have as much time to kind of build up the pipeline, so to speak, of the oxidative phosphorylation, that takes a bit of time to get the oxygen coming in and so forth.

They tend to have fewer mitochondria and require less of an oxygen supply and rely more on glycolysis, which are those initial steps of the extraction of energy from glucose, but which can happen sort of more quickly. They also tend to be larger in cross-sectional area because that allows them to generate more force. The cost of this is lower endurance because basically they use up their energy supply more quickly and therefore need to be rested for a time before they recover. This then leads us into talking a little bit about muscles and exercise. So I will talk more in the future about exercise and health physiology and so forth. I'll just make a few brief remarks here about the connection between this and muscle physiology in particular. So the phrase muscle hypertrophy is used to

refer to the increase in size and mass of skeletal muscle over time. And this occurs through the growth in size of its component cells. So basically what happens as you exercise and train is that the muscles get bigger. There are multiple ways that this can happen, depending on the type of training that you engage in. So one type of muscle hypertrophy is called sarcoplasmic hypertrophy, and that essentially results in an increase in the ability of the muscle to store glycogen and other energy stores, and that tends to result largely from anaerobic exercises. The other type of hypertrophy is referred to as myofibrillus hypertrophy, and that relates to an increase in the size of the myofibrils, effectively an increase in the number and density of the filaments that make up the

myofibrils, which remember the organelles that actually perform the contraction. Now, a corollary of muscle hypertrophy is muscle fatigue. So this is the decline in the ability of muscles to generate force, which occurs over time as a result of vigorous exercise. Muscle fatigue has a number of causes, including fatigue of the actual nerves that innovate the muscle cells, but also due to factors internal to the muscles. So this includes shortage of fuels that are gradually used up, especially in the fast-twitch muscles that need to be replaced, and accumulation of metabolic byproducts that interfere with the contraction of muscles and that need time to clear.

One of the major metabolic byproducts of muscle activity in the absence of sufficient oxygen is called lactic acid. Lactic acid is a metabolic byproduct of glycolysis that does not then go on to extract all of the possible energy through oxidative phosphorylation. So this happens when there's insufficient oxygen to undergo oxidative phosphorylation, and instead the metabolic byproduct of lactic acid is produced, and that will build up in the muscles if it's not able to be removed rapidly enough, and that causes muscle fatigue and sort of a sore burning sensation in the muscles, and it takes some time to be cleared out by the bloodstream following vigorous exercise. I'll talk more about some of the details of that when we get to the series on biochemistry

and the different metabolic pathways of the body. A similar notion to muscle fatigue, or a closely related notion at least, is that of oxygen debt. So oxygen debt is a measurable increase in the rate of oxygen intake, particularly by the muscles, following strenuous activity.

So typically what happens is that when the activity rate, the contraction rate of muscles is increased, it takes some time afterwards for the oxygen supply to be sufficiently increased by the bloodstream. There's a need for increase. blood flow and that takes some time to happen. As a result, there is an oxygen debt which is built up,

an oxygen deficit, because there was a time when initially as exercise is ramping up, that muscle cell doesn't have sufficient oxygen to replenish that which is used up. And in cases of extremely vigorous activity, actually, there may never be a time when the oxygen is able to be replenished at a sufficiently fast rate. And if that's the case, then the oxygen debt will just be continually increased. either of those cases what will happen eventually when exercise is terminated, then there will be a time when oxygen consumption goes down very quickly, but the rate of oxygen consumption doesn't go down to zero immediately. There's a time when gradually the oxygen consumption goes down as the deficit

that was built up during the exercise period is gradually made good. This is the recovery time following vigorous exercise. When oxygen usage is higher than baseline, even though the consumption of oxygen by the muscle tissue is actually fairly low. It's because there needs to be a time of recovery when metabolic reserves of ATP and also creatine phosphate are replenished. This leads me to talking about creatine phosphate because I've talked about ATP many times before. That's sort of like the energy currency of the cell, the most immediate form of energy usage. We've talked about how ATP is necessary to provide energy for the power stroke of the myosin interacting with the thin filament. but I haven't mentioned creatine phosphate.

And it's quite important in understanding the energy supplies and storage of muscles. So I'll just talk about it briefly here. Again, more about this when we get to talking more about some of the metabolic pathways and energy consumption in the body. But creatine phosphate is a phosphorylated form of an organic compound called creatine. And phosphorylated just means that it's got phosphate groups added to it. And these high-energy phosphate groups, you can think of them as compressed springs that represent sort of a high energy molecule that's ready to be extracted and release energy. ATP has three of these phosphate groups, but creatine phosphate has a number of them as well.

So it's a phosphorylated form of creatine, and it serves as a what's called a rapidly mobilizable reserve of these high-energy phosphates. So basically, creatine phosphate serves as a storage for these phosphates that can be used to create ATP very quickly. Creatine is transported through the blood and taken up by tissues that have high energy demands, such as muscles. Muscles are not able to store very high quantities of ATP for complex reasons we didn't get into here. So to give them some kind of extra energy storage capacity, they have these supplies of creatine phosphate, which is able to serve as a ready reservoir of extra ATP. But of course, eventually those two will be depleted, and then the balance needs to be made

up by production of new ATP through oxidative phosphorylation, which requires oxygen brought in from the bloodstream. So typically what happens when a muscle cell first begins contracting, so utilizing a lot of energy, initially it will utilize its ready supply of ATP, and that's the most readily accessible form of energy. Once those begin to be depleted, new ATPs will start to be produced from creatine phosphate, which is a ready store of these phosphates to replenish those used up in the process of contraction. Once the readily accessible phosphates and creatine phosphate begin to be depleted, new ATP begins to be produced through glycolysis. So that requires glucose be brought into the cell through the bloodstream,

and glucose is then broken down, and that process produces some amount of ATP. That process, however, is known as anaerobic respiration because glycolysis itself does not require oxygen. If there is insufficient oxygen available, as is often the case when exercise immediately starts, because breathing takes a while to increase. Or if exercise is extremely vigorous and there's just insufficient availability of oxygen in the body, then the cell will have to rely on this anaerobic respiration. And that's when you have the buildup of lactic acid

that I mentioned before. The downside to that is that, apart from the buildup of lactic acid, you also just don't have as much energy production available because most of the energy that is contained in glucose has not been extracted. You can get a little bit out of it through anaerobic respiration, through glycolysis itself, but not very much.

The real source of energy that's able to really replenish this supply of ATP is oxidative phosphorylation, which occurs in the mitochondria. This requires blood glucose to break down as the ultimate source of energy, but also it requires oxygen, which is the electron acceptor, which takes in the low energy electrons after they've been passed through the electron transport chain. And this produces very large amounts of ATP and can continue for a very long period of time. The big downside, of course, is that it takes a while to kind of get going and build up. It requires a constant source of glucose as well as a constant source of oxygen.

It also produces a large amount of heat, which is why we warm up very quickly when we're engaging in vigorous aerobic exercises because of all of this oxidative phosphorylation, at least that's a major contributing factor. So there's sort of different tiers of energy sources of muscles, starting with ATP and then creatine phosphate, anaerobic respiration using glycolysis and then at the kind of bottom level is orobic respiration using the oxidative phosphorylation in the mitochondria. And so cells will begin to access the most readily, the easiest, most readily available form of energy first and then sort of work their way down. And as I mentioned before, of course, the two different types, the fast switch and the slow twitch

muscles differ in the tendency they have to utilize one source versus the other of energy. the slow twitch muscles preferring the higher energy and sort of longer term more sustainable energy source of the aerobic respiration, but at the expense of less sort of immediate high intensity force generation, whereas the fast-risk muscles have that greater ability to exert strong forces for a shorter period of time, but at the expense of not being able to utilize as much of the energy extracted from glucose in the form of aerobic respiration, instead relying more on anaerobic respiration and also ready storage of creatine phosphate. All right, so that's a little bit about exercise and energy storage in muscle cells. Now, before we finish out this episode, I just want to kind of summarize a bit and make sure

that we've sort of fully understood the process of the muscle contraction in particular, because that is sort of at the core of what I wanted to convey in this episode. To consolidate that, let's step through the process of muscle contraction one more time, beginning first at the motor neuron, which brings an action potential, stemming from the brain or the spinal column or whatever it comes from, it carries that electrical signal to the axon terminal, which is at the kind of interface muscle cell itself. The action potential causes vesicles containing acetal coline,

a neurotransmitter, to be released. The acetal coline diffuses across the membrane, diffuses across the synaptic cleft, and then binds to receptors on the membrane of the muscle cell, Those receptors then open connected ion channels which trigger an action potential, so a change in the voltage potential, across the membrane of the muscle cell. This action potential in the muscle cell now, or muscle fibres is also called, then propagates along the cell membrane of the muscle cell, which is also called the Sarko lemma, it's got a special

name. So it propagates along the cell. Remember, muscle cells are very long and kind of thin, and they also have a little. these sort of tunnels, sort of crossways extending from one side to the other, which are called T-tubules. And these T-tubules help the action potential propagate quickly throughout the both the surface and sort of the interior of the muscle fibre. Now this is important because this action potential, as it reaches different parts of the muscle fiber, causes calcium ions, which normally are stored inside a special organelle called the sarcoplasmic reticulum. This is a membrane

bound interconnected web of sacks and membrane segments, which is a special version of the endoplasmic reticulum, which is normally found in regular ucharotic cells. So this psychoplasmic reticulum is sort of extended throughout the interior of the cell. And as the axi potential propagates around, this causes a release of these calcium ions by the psychoplasmic reticulum. That's why it's so important to ensure that these t-tubules carry the electrical signal across different parts of the cell at more or less the same time to ensure that calcium release is synchronized throughout the muscle fiber and therefore to ensure that the process of contraction itself is synchronized throughout the muscle fiber. So these calcium ions, as they diffuse out from the sarcoplasma

reticulum into the cytosol, they diffuse and come into contact with the other sort of key special organelle of muscle fibers. And these organelles are called the myofibrils or fibrels, as I've often called them. They're basically very long sausage-like structures, which can of a number of sarcomeres laid end to end. A sarcomere is kind of like the fundamental contracting unit of a muscle fibre. And each of these myofibril organelles, surrounded by the sarcoplasmic reticulum, has many of these sarcomeres kind of laid end to end. Each of the sarcomeres consists of two different types of filaments, or myofilaments as they're also called, so the thick and the thin filaments. What happens is that when the calcium diffuses, it binds to a special binding site

called, well, binding protein actually, called troponin, which is located on the thin filament. So it binds to this special site on the thin filament, causes another protein to kind of shift in place, which opens up binding sites on the thin filament. These binding sites on the thin filament then allow special regions of the thick filament, the myosin thick filament, as opposed to the actin thin filament, if you recall, there's the thin and the thick, actin and myosin. The myosin heads, which are kind of analogous in shape to ear cleaners, but with the head bit kind of bent backwards to some extent, these myocin heads are then able to bind to the mycine

now that the space has been cleared for them by the calcium binding. These myocin heads progressively bind, bend backwards, unbind, bend forwards, then bind again, bend backwards, unbind, bend forwards, and so on and so forth in a process that's powered by ATP and is called a power stroke. So each of these cycles is called a power stroke, And a single nerve impulse, which will trigger a single muscle twitch, will generate maybe 20 or so of these power strokes before the calcium ions are cleared from the cytosol and go back into the sarcoplasmic reticulum. And therefore, the binding sites for the mycine are covered up again and the power stroke stops.

But while the power stroke is going, what happens is that the thick and the thin filaments are pulled relative to each other. And that has the effect of essentially pushing the parallel segments of thin filaments towards each other and in towards the thick filaments, which are kind of arrayed in the center. Remember there's kind of the set of thin filaments on the edge and then the thick filaments in the center and then the thin filaments on the other side. And the power strokes result in the pushing inwards of the thin filaments so that they move towards each other and towards the set of thick filaments in the center, resulting in the sarcomere shrinking in size, decreasing in length. and that's called a muscle contraction. As the sarcomere contracts in length, the whole myofibiral contracts in length, and that occurs in all of the myofibrils in the muscle fibres, so the muscle fiber contracts in length,

and of course that happens in many muscle fibers at once, so the whole muscle contraction length, and that results in a force that pulls on the tendon, which is connected to the muscle tissue, the contractive tissue itself, which then pulls on the bone, and results in a force being applied to that bone. So this is the overall process of how muscle contraction works in skeletal muscles. And it's all ultimately powered by ATP, triggered by neuronal signals with an intermediary

of calcium to transmit the signal directly from essentially the outside of the cell to the myofilaments themselves. And the ultimate physical action that actually does the moving is this power stroke of the mycine head on the thick filament binding to special binding sites on the thin filament, bending backwards, which pulls them relative to each other, detaching, bending forwards again, so readies for another stroke, then binding once again, bending backwards, which pulls them relative to each other once again. It keeps attaching, pulling and detaching in a process that requires ATP and requires calcium to ensure that the binding site is available, but other

than that, it'll sort of keep going as long as those, the energy and the calcium is available. So it's quite a remarkable process, really, and I think is just fascinating that evolution has been able to involve such a ingenious mechanism for producing movement on a large scale. All right, so that concludes what I wanted to talk about today. In the next episode, I'm going to discuss motor control. So here we've talked about the process of how muscles contract and some of the metabolic aspects of that, but we haven't really talked about how motor actions are controlled and regulated, particularly at a high level by the brain. So that's what we're going to cover in next week's

episode. Also, I have a special announcement. For a long time, I've been intending to bring this podcast to, well, new audiences as far as I can, and one way of doing that that I've been thinking about is to bring the podcast to YouTube. Doing so, however, is going to require quite a lot of editing work. I need to convert all of the 150-odd episodes in the backlog to a video form, and I also want to add at least a minimal kind of visual content to it. So say, pictures and diagrams to accompany some of what I'm saying. And then they need to be uploaded to the channel that I've created and so forth. And that's going to take a lot of time.

And so in order to sort of facilitate this, I'm thinking about hiring someone to assist me with this editing and uploading process. Ideally, I'd love to be able to hire one of my listeners or possibly even multiple listeners to help me with this. The point is, if anyone who is listening would be interested in helping out with this, it doesn't really require that much in the way of editing experience. It's not that difficult, but it's more just something that will take time and a bit of patience, I suppose. But if you are interested, please send me an email. My email address is FODs12.gm.com. That's FODDS12 at gmail.com. Also, feel free to email me with any questions, suggestions, or other feedback from the podcast. Love to hear from my listeners. If you would like to support,

the show, you can make a donation either via PayPal as a one-off or you could become a patron on Patreon. You can just Google Patreon Science of Everything podcast if you would like to sign up as a patron there. Thanks once again for listening. Hope you enjoyed this episode and I'll talk to you next time.