Welcome back. We recently talked about the somatic nervous system, which controls skeletal muscle. Now we're going to talk about how muscle contraction occurs. In this title slide, this image is a light microscope image of skeletal muscle. You can see how it has these little stripes, which are striations, We'll talk about how these are important for the contraction of muscle, in particular skeletal muscle. So we're going to have two videos about skeletal muscle. 9
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In this first one, we're going to talk
about all three muscle types very briefly, and then we're going to talk about some general principles of muscle contraction. Then we'll move into discussing skeletal muscle structure, and how contraction occurs. Then in the second session, we'll focus on how tension is formed, and some of the characteristics of tension, as well as some principles about muscle metabolism. There are three main types of muscle in the body. Of course, today we're going to be talking about skeletal muscle, which is also called striated muscle because it has these stripes. Skeletal muscle fibers, or cells, you can use those terms interchangeably, are going to be quite large, both in diameter, and often in length. A skeletal muscle cell or fiber extends the entire length of a muscle. They're going to be very large, and they're actually going to be multinucleated. They have many nuclei. That's what most of these are. You can see in this diagram, they're at the edge of the cell or fiber. Then of course it's going to be controlled by the somatic nervous system. Dr. Jakoi is going to tell you about cardiac muscle, which is also striated, meaning it also has those stripes that you can see in the microscope. The stripes are due to the alignment of the myosin and actin filaments. The cardiac muscle fibers are much smaller than skeletal muscle fibers, both in diameter and length. However they're going to have specialized junctions between the cells that allow the cardiac myocytes to contract as a functional unit. So that the whole heart will contract essentially as one. She will tell you much more about that. Their function is modulated by the autonomic nervous system. She will also discuss briefly, smooth muscle, which is present in many organs in the body. These muscles are going to be different. Smooth muscle cells are not striated. They still contain myosin and actin, but they're not organized in such a way that you can see it on a microscopic level. They won't have those stripes in the microscope. They're also relatively small cells, often spindle-shaped. Again, they're very often going to function as a sheet of cells. To do that, they will have tight junctions, or strong junctions, between the cells that will allow them to adhere to one another as they're contracting, so that they can act as a unit. Again their action, or their amount of activity or contraction, will be regulated by the autonomic nervous system. Let's briefly talk about some of these shared principles between the three muscle types.. In all three cases, we're going to have myosin filaments, which are a type of motor protein. Myosin is going to bind to and move actin filaments to shorten the muscle cell. This is how we get contraction. The difference will be in how organized that network of myosin and actin will be, in whether or not you see striations in the cells as in cardiac and skeletal muscle, versus not being able to see striations in smooth muscle. Of course we're going to want this contraction to be regulated. In all three cases, it's going to be regulated by calcium ions. The manner will be slightly different, or radically different, between the three muscle types. We'll be talking about that in the future. Then at least in some cases, if not all cases depending on the muscle type, what leads to contraction are changes in membrane potential. This is called excitation-contraction coupling. We'll be talking more specifically about how that happens in each of the muscle types. So let's move now to more specifically talk about skeletal muscle. We've already said that the muscle itself is going to be made up of many muscle cells, or fibers. You can use that term interchangeably. Here's a cross-section of a muscle. You see that if we zoom in on a single muscle cell or fiber, and then that cell or fiber is composed of many other units called myofibrils. That's what's shown here. If we zoom in and look at a single myofibril, that is going to be composed of many molecules of actin and myosin. So there are a number of myofibrils in a muscle cell. That number determines the force that the fiber can generate. The myofibril is the functioning unit within the cell that is contracting. Along its length, the myofibrils can be divided into sarcomeres, as shown in here. So that a muscle cell is made up of many myofibrils that are in parallel. A myofibril is composed of many sarcomeres that are in series. There'll be hundreds, if not thousands, of sarcomeres that make up a single myofibril. It's going to be each sarcomere that contracts. So if you've got many sarcomeres that are contracting at the same time, then you're going to have a shortening of the muscle fiber., This will cause an action, which we'll be talking more about. It's the number of myofibrils that determine the force generating capability of the fiber. We can divide the myofibril into sarcomeres. The sarcomere pattern is going to be what causes the striations, or the banding, of the skeletal muscle cells, The myofibrils are aligned in a very organized way. That's what we're going to start talking about now. At the top of this image we have an electron micrograph of a portion of a myofibril. It shows a single sarcomere. You can see that it's got a light portion, and a dark portion, and that those are alternating. So that if we had many sarcomeres, you would see alternating light and dark. This light and dark pattern is responsible for the striations. Below that image, we can see what are the fibers or filaments that are causing that pattern. We have these Z lines are the ends of the sarcomere, they determine the borders between the sarcomeres. Sticking out of each Z line are a set of thin filaments, which are actin. Actin is the protein that comes out of the Z lines. One set of actin for each sarcomere faces the other set of actin. Then interdigitated between those actin filaments, between those thin filaments, are going to be thick filaments. This is th myosin. The myosin is going to have motor properties. The myosin will walk towards each Z line. This end of the myosin will walk towards this Z line, and this end of the myosin will walk towards this Z line. Because the myosin filaments are thick, then they appear at these dark bands. We call that the A band. You can remember that dark has an A in it, and so it's the A band. Anywhere where we have myosin, since it's thick, it will be staining darkly. That's what's responsible for this A band right here. This is where myosin is. The actin is going to be staining more lightly; it's thinner. You can remember that the I band is where it's light. Light has an I in it. That's going to be where there is only actin. So the I band, this lighter staining portion, will be where there is only actin. As soon as you get myosin, then it's going to be darkly staining. It's going to be the A band. So let's see what happens when we have contraction. Thhis is shown on this next diagram. In this diagram we've got our Z lines. Right here. This is going to be the borders of our sarcomere. So we've got one sarcomere here. We've got our actin filaments, our thin filaments shown in blue, that emanate from the Z lines, heading towards the middle of the sarcomere. Then in red in this diagram, we have myosin. You can see these little circle structures. , These are the heads of myosin that are going to be walking along the actin. The image also shows a protein called titin, which anchors myosin into the sarcomere. But it does not preventing it from walking towards the Z lines. So we have these symmetrical myosin filaments. They are each walking towards Z lines, causing the sarcomere to get shorter. Our A band would be the whole length of the myosin. Our I band, as is shown, is where there's only actin. So, as myosin walks toward the Z lines, then there's a shorting of the I band as contraction occurs. However, that A band stays the same width. Myosin is not changing in length. What's changing is the amount of actin that is alone, because the myosin and actin become more interdigitated. So that means the I band will be reduced in width during contraction, but not the A band. It's important to understand that it's not the length of these molecules that's changing. It is the amount of interdigitation that's changing. So, let's talk now with more detail about how this is occurring. We've already said that contraction is regulated by calcium. How is this going to happen on a molecular level? We're going to look here at the top, which is actin, our thin filaments. you can see that there's another structure on actin called tropomyosin and troponin. Tropomyosin is running in parallel along the actin. It's binding actin at the site where myosin would bind. So tropomyosin is preventing myosin from binding actin when there is no calcium around. With an increase in calcium, the calcium binds to troponin which is made up of several troponin molecules. The binding of calcium to troponin will cause a change in its confirmation that causes tropomyosin to be removed from the myosin binding sites on actin. We have an effect of calcium on the actin. This is in contrast to calcium modifying myosin in smooth muscle. So that will, shown down here below, we see myosin can now bind actin. Calcium binds troponin which then move tropomyosin out of the way. That’s how calcium regulates contraction, We'll talk more about this very soon. What's going to be required in order for the actual contraction to occur? Once we have allowed myosin to bind actin, we're going to require ATP as an energy source. Myosin is an ATPase. Without ATP, this myosin head emanates from the thick filament here. Here's actin. In red is tropomyosin. You can see how it's now moved out of the way. We have calcium present. But in this first state we're seeing, the rigor state, where there no ATP bound to this particular head. This means that the myosin head is tightly bound to actin. That's call the rigor state. It's when there's no ATP bound then myosin is tightly bound to the actin. You can remember this because this is the reason for rigor mortis, which is when if a person dies. They quickly use up their ATP in their body. As a result, the myosin will now tightly bind actin. That causes the stiffness of the muscles characteristic of someone who has recently passed away. Eventually, the proteins of the muscles will be broken down so then rigor mortis will no longer be happening. At least for the short time after death, rigor mortis happens because of this rigor state when there's no ATP bound to the myosin head. Eventually, ATP will bind. That is going to cause myosin to let go of the actin filament. Then ATP Hydrolysis will occur. That will cause the myosin head to now ratchet forward. And then it will bind. Then there will be a release of inorganic phosphate that will cause what's called the power stroke. That's a ratcheting of the myosin head that is going to then cause it to have walked closer to that Z-line, in order for contraction to occur. Then ADP will be released, and we will be back to the rigor state. So it's going to be a matter of being bound in the rigor state, binding ATP and having the myosin head let go. Then having ATP hydrolysis, ratcheting, moving closer to the Z-line, and then having inorganic phosphate be released. That is the power stroke. Now myosin is that much closer to the Z-line. The cycle will continue and continue. Keep in mind that when this particular myosin head lets go during the cycle, that's okay, it's not like we're going to go back to a relaxed state. Because in this thick filament, we have many, many myosin heads acting on the actin nonsynchronously. So that when one head has let go, there'll be another head in a different part of the cycle attached. That's how we can have a continual contraction and ratcheting closer and closer to the Z-lines. Even when individual heads are no longer bound to the actin because of where they are in the cycle. So this means that what we're need for contraction is ATP. Which we are going to assume is present, really, in all circumstances. We'll talk about the sources of that ATP in the next lecture. We are going to need calcium so myosin can bind actin in the first place. So now let's link what we know is excitation from the somatic nervous system to contraction which requires an increase in calcium. Keep in mind that we're going to have our somatic motor neuron that's sending a branch of its axon, to synapse onto a spot on the skeletal muscle fiber or cell. That somatic motor neuron will release acetylcholine, as soon as an action potential travels down to the synapse. The acetylcholine will bind nicotinic acetylcholine receptors on the skeletal muscle plasma membrane. This will cause some sodium to enter at that point of the skeletal muscle membrane. It causes a graded potential. The important thing to remember, as we've said before with the skeletal muscle plasma membrane, it's basically going to be totally covered in potassium and sodium voltage-gated channels. So the whole membrane will be able to have an action potential. So if we have a small graded potential at the synapse between the neuron and the muscle, we are going to cause an action potential. Because we're having a grade potential right next to a bunch of voltage-gated channels. So for all intents and purposes, every time that neuron fires an action potential, we're going to have an action potential in the skeletal muscle membrane. That action potential will, as I said, travel along the whole length of the skeletal muscle membrane. And it also travel down special invaginations of the plasma membrane, called transverse tubules. Transfers because they're at 90 degrees from the plasma membrane. This brings the action potential into the muscle fiber. On the next slide we'll see another view of that. In between these T tubules is the sarcoplasmic reticulum of the skeletal muscle. This is the muscle-specific form of the endoplasmic reticulum that stores calcium. This sarcoplasmic reticulum is going to be in very close vicinity to the T tubules. As show in this window down here, we have to bring together two different membrane proteins. The first is the dihydropyridine receptor, which is sitting in the T tubule membrane. Thhis is actually a voltage gated calcium channel. However, it's slow to open. The really important aspect of this receptor for this process is that it's voltage gated. Which means that when that action potential travels down that transverse tubule, it's confirmation is going to change. iitting, actually touching, a second receptor that's sitting in the sarcoplasmic reticulum, the ryanodine receptor. So the change in confirmation of the dihydropyridine receptor, in response to the action potential, is going to cause a change in the confirmation of the ryanodine receptor. This change lets calcium leave the sarcoplasmic reticulum and enter the cytosol. These two proteins, you'll also hear about from Dr. Jakoi in the heart. But in the heart they won't necessarily be physically coupled. So there will be a difference in how this system works for the cardiac system. But you'll still hear about these same two membrane proteins from Dr. Jakoi. The calcium rushing into the cytosol is then going to bind to the troponin. This will cause tropomyosin to be removed from the myosin binding sites on actin. This allows myosin to bind actin. However, as soon as calcium starts rushing into the cytosol, we're also going to activate the sarcoplasmic reticulum calcium ATPases. Which are also called SERCA. These will start to pump calcium back into the sarcoplasmic reticulum. We'll talk more about that in terms of what that means for contraction. , Basically very soon after we start dumping calcium, we're going to start putting it back into the SR. This is going to allow for relaxation. This diagram shows just a small portion of a skeletal muscle cell. We have the plasma membrane in yellow, as well as the T tubule shown in yellow. Then we see just two myofibrils, that are sitting right underneath the muscle plasma membrane. Then we have in blue the sarcoplasmic reticulum, that is running between the two T tubules. So you can see how the sarcoplasmic reticulum is wrapping around these myofibrils. Once the action potential travels and we get our E-C Coupling, the myofibril will be bathed in calcium coming from the sarcoplasmic reticulum. Then the sarcoplasmic reticulum will also be in a good spot to reuptake that calcium. You can see how these T tubules continue into the muscle fiber or cell. They bring that action potential all the way into the center of this fairly large cell. This gives an efficient Excitation-Contraction Coupling. Which is essential for having that whole muscle cell contract in a coordinated fashion. Okay, so we now talked about how we're going to have, in all muscles, actin and myosin and they're going to slide along one another. Myosin is going to, since it's a motor, walking along the actin to shorten the filament network. This shortens the cells, and generates force. We'll be talking more about that. So we form cross bridges, that's myosin heads binding the actin as they cycle. This process uses ATP. Then, we're going to couple the action potential coming from the neuron and then traveling throughout the muscle plasma membrane to an increase in cytosolic calcium ions. In skeletal muscle, we're going to have an actin-based control system where calcium binds troponin. Which then moves tropomyosin on the actin. Then we're going to have removal of calcium through the actions of the SR calcium ATPase.
