Welcome back. We recently talked about the somatic nervous system, which is going to control skeletal muscle. And 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. And you can see how it has these little stripes, which are striations. And we'll talk about how these are important for the contraction of muscle, and in particular, skeletal muscle. So we're going to have two videos about skeletal muscle. And 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. And then we'll move into talking about skeletal muscle structure and how contraction occurs. And 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. So they are going to be three main types of muscle in the body. Of course, today we're going to be talking about skeletal muscle, which is also striated, 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. Because a skeletal muscle cell or fiber is going to run the entire length of a muscle. So they're going to be very large, and they're actually going to be multinucleate. They're going to have many nuclei. That's what most of these are that you can see in this diagram. And they're at the edge of the cell or fiber. And 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 because of the alignment of the myosin and actin filaments. These cardiac muscle fibers are going to be much smaller than skeletal muscle fibers, both in diameter and length. However, they're going to have specialized junctions between the cells that are going to allow the cardiac myocytes to contract as a functional unit so that the whole heart will contract essentially. And so she'll be telling you much more about that. And their function is going to be modulated by the autonomic nervous system. Then there she will also discuss, briefly, smooth muscle, which is going to be present in many organs in the body. And these are going to be different because 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. And so they won't have those stripes in the microscope, and they're also going to be relatively small cells, often spindle-shaped. And again, there are very often going to function as a sheet of cells. And to do that, they will have tight junctions, or strong junctions, between the cells that will allow them to adhere to one another as their contracting so that they can act as a unit. And again, their amount of activity or contraction will be regulated by the autonomic nervous. So let's briefly talk about some of these shared principles between the three muscle types. Where in all three cases, we're going to have myosin filaments which are going to be a type of motor protein that are going to bind to and move actin filaments to shorten the muscle cell. And so 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 you do 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. And 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. And we'll be talking about that in the future. And then, at least in some cases, if not, all cases, depend on the muscle type, what is going to lead to contraction are changes in membrane potential. And so this is called excitation-contraction coupling. And we'll be talking more specifically how that happens in each three of the muscle types. So let's move in now to more specifically talking about skeletal muscle, where we've already said that the muscle itself is going to be made up of many muscles cells or fibers. You can use that term interchangeably. So here's a cross-section of a muscle. And you see that we are going to zoom in on a single muscle cell or fiber. And then that cell or fiber is composed of many other units called myofibrils. And that's what's shown here, where we can zoom in and look at a single myofibril that is going to be composed of many molecules of actin and myosin. So it's going to be the number of myofirbrils in a muscle cell that is going to determine the force that it can generate. So the myofibril is kind of the functioning unit within the cell that is contracting. And along its length, myofibrils can be divided into sacromeres, which is what shown in here. So that a muscle cell is made up of many myofibrils that are in parallel, and then a myofibril is composed of many sacromeres that are in series. So they'll be hundreds if not thousands of sarcomeres that are making up a single myofibril. And it's going to be each sarcomere that is going to contract. And so if you've get many sacromeres that contracting at the same time, then you're going to have a shortening of the muscle, which will cause an action. Which we will be talking more about. So it's the number of myofibrils that are going to determine the force generating ability of the fiber. And we can divide the myofibril into sarcomeres. And the sarcomere pattern is going to be what's going to cause the striations or the banding of the skeletal muscle cells. Because the myofibrils will be aligned in a very organized way. So that's what we're going to start talking about now. Wherein at the top of this image, we have an electron micrograph of a portion of a myofibril that's showing you a single sarcomere. And 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 and light and dark. And this is going to be responsible for the striations. Then below that image, we can see what are the fibers or the filaments that are causing that pattern, where we have these Z lines which are the ends of the sarcomere. They determine the borders between the sarcomeres. And sticking out of each z-line are a set of thin filaments, which are actin. Which are going to be proteins that are coming out of the Z lines. One set for one sarcomere are going to be kind of facing each other. And then interdigitated between those actin filaments, between those thin filaments, are going to be thick filaments, which are going to be the myosin. And so the myosin is what's going to have the motor properties, and the myosin is going to walk towards each Z line. So 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 are going to appear as these dark bands. And so we call that the A band. And you can remember that that dark has an A in it, and so it's the A band. So anywhere where we have myosin, since its thick, it will be staining darkly. And that's what's responsible for this A band right here, is that this is where myosin is. Then actin is going to be staining more lightly, and it's thinner. And so you can remember that the I band is where it's light, and 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, and it's going to be the A band. So let's see what happens when we have contraction, which is what's shown on this next diagram. Where in this diagram, we've got our Z lines, right here. So this is going to be the borders of our sacromeres. So we've got one sarcomere on here. We've got our actin filaments, are thin filaments are in shown in blue, that are emanating from the Z lines, heading towards the middle of the sarcomere. And then in red, in this diagram, we have myosin. And you can see these little circle structures which are the heads of myosin that are going to be walking along the actin. And it's also showing a protein called Titin, which is anchoring myosin into the sarcomere, but not preventing it from walking towards the Z lines. So we've got these symmetrical myosin filaments that are each walking towards Z lines, causing the sarcomere to get shorter. So our A band would be the whole length of the myosin. And our I band, as it's shown, will be where there's only actin. And so as mysoin walks towards the Z lines, then that is going to shorten the I band, As contraction occurs. However, the A band is going to stay the same width. Because myosin is not changing in length. What's changing is the amount of actin that is alone. Because the myosin and actin are becoming more interdigitated. And so that means that it's the I band that is going to be reduced in width during contraction, but not the A band. And then 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 more with more detail about how this is occurring. And we've already said that the that contraction is going to be regulated by calcium. And so how is this going to happen on a molecular level? And so we're going to look here at the top, which is actin, our thin filaments. And you can see that there's another structure on here called tropomyosin and troponin. Tropomyosin is running in parallel along the actin. And 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 will bind to troponin, which is made up of several troponin molecules. And the binding of calcium to troponin will cause a change in its conformation that causes tropomyosin to be removed from the myosin binding sites on actin. So we have an effective calcium that is acting on the actin. And this is going to be in contrast to calcium modifying myosin in smooth muscle. So down here below, we're seeing myosin, which will now be able to bind once calcium binds to troponin, which will then move tropomyosin out of the way. So that's how calcium is going to regulate contraction. And we'll talk more about this very soon. Then what's going to be required in order for the actual contraction to occur once we have allowed myosin to bind actin, is that we're going to require ATP as an energy source. So myosin is going to be an atpase. Without ATP, this is a myosin head that's emanating from the thick filament here. Here's actin, and you can in red is tropomyosin, and you can see how it's now moved out of the way. We have calcium present. But in this first state that we're seeing, the rigor state, there's no ATP bound to this particular head, which means that the myosin head is tightly bound to actin. So that's called the rigo state. It's when there's no ATP bound and it's 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. And so as a result, the myosin will now tightly bind ATP, and that causes the stiffness of the muscles that are characteristic of someone who has recently passed away. Eventually, the proteins of the muscles will be broken down so that then rigor mortis will no longer be happening. But 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. And that is going to cause myosin to let go of the actin filament, and then ATP hydrolysis will occur. And that will cause the myosin head to now ratchet forward. And then it will bind, and 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 up closer to that Z line in order for contraction to occur. And then ATP will be released, and we'll 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. So we have a ratcheting closer to the Z line. And then having the inorganic phosphate be released so that we have the power stroke. And so now, the myosin is that much closer to the Z line and the cycle will continue and continue. Keep in mind that when this particular myosin head let's go during a 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 non-synchronously. So that when one had has let go, they'll be another head in a different part of the cycle. And so 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 going to need for contraction is ATP, which we're going to assume is going to be present really in all circumstances. And we'll talk about the sources of that ATP in the next lecture. And then we're going to need calcium so that myosin can bind actin in the first place. So now let's link what we know is going to be the excitation from the somatic nervous system to contraction, which is going to require an increase in calcium. So keep in mind that we're going to have our somatic motor neuron that's sending a branch of its axon that is going to synapse onto a spot of the skeletal muscle fiber or cell. And that the somatic motor neuron is going to be releasing acetylcholine as soon as an action potential travels down it. And the acetylcholine will bind nicotinic acetylcholine receptors on the skeletal muscle plasma membrane, which will cause some sodium to enter at that point of of the skeletal muscle membrane. So it's going to cause a graded potential. The important thing to remember, as we've said before, with the skeletal muscle plasma membrane, is that it's basically going to be totally covered in potassium and sodium voltage-gated channels. So that the whole membrane will be able to have an action potential. So that 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 that 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. So that action potential will, as I said, travel along the whole length of the skeletal muscle membrane. And then also travel down special invaginations of the plasma membrane called transverse tubules. Transverse because they're at 90 degrees from the plasma membrane. And this is going to bring the action potential into the muscle fiber. And on the next slide, we'll see another view of that in between. In between these T-tubules is going to be the sarcoplasmic reticulum of the skeletal muscle, which is going to be a muscle specific form of the endoplasmic reticulum that stores calcium. This sarcoplasmic reticulum is going to have to be in very close in vicinity to the T-tubules because, as shown in this window down here, we have to bring together different membrane proteins. The first is the dihydropyridine receptor, which is sitting in the T-tubular membrane, which is actually a voltage-gated calcium channel. However, it's slow to open. And so the real important aspect of this receptor for this process is going to be that it's voltage-gated. Which means that when that action potential travels down that transverse tubules, its conformation is going to change. And it's actually touching a second receptor that's sitting in the sarcoplasmic reticulum, the ryanodine receptor. So the change in conformation of the dihydropyridine receptor in response to the action potential is going to cause a change in the conformation of the ryanodine receptor, which then let's calcium leave the sarcoplasmic reticulum and enter the cytosol. These two proteins, you'll also hear about from Dr. Jakoi in the heart, but they they won't necessarily be physically coupled. And so there will be a difference in how the system works for the cardiac system, but you'll still hear about these same two membrane proteins from Dr. Jakoi. So the calcium rushing into the cytosol is then going to bind the troponin and then cause tropomyosin to be removed from the sites and actin, which then allow myosin to bind actin. However as soon as calcium starts rushing into the cytosol, we're also going to activate sarcoplasmic reticulum calcium atpases, which are also called SERCA. Which will start to pump calcium back into the sarcoplasmic reticulum. And we'll talk more about that in terms of what that's going to mean for contraction. When basically very soon after we start dumping calcium, we're going to start putting it back into the SR, which is going to then allow for relaxation. So this diagram is showing you just a small portion of a skeletal muscle cell. Where we have the plasma membrane in yellow as well as the T-tubules shown in yellow. And then we're seeing just to myofibrils that are sitting right underneath the muscle plasma membrane. And then we have in blue, the sarcoplasmic reticulum that is running between the two T-tubules. And so you can see how the sarcoplasmic reticulum is wrapping around these myofibrils. So that once the action potential travels and we get our E-C coupling, the myofibril is going to be bathed in calcium coming from the sarcoplasmic reticulum. And then the sarcoplasmic reticulum will also be in a good spot to then reuptake that calcium. And you can see how these two tubules are just going to continue into the muscle fiber or cell, which is going to bring that action potential all the way into the center of this fairly large cell in order to have efficient excitation contraction coupling. Which is going to be essential for having that whole muscle cell to contract in a coordinated fashion. Okay, so we've now talked about how we're going to have an all muscles, actin and myosin. And they're going to slide a long one another because the myosin is going to, since it's a motor, be walking along the actin to shorten the filament network. Which is then going to shorten the cells. And that's going to generate for us, and we'll be talking more about that. So we're going to form cross bridges. That's going to be those myosin heads binding the actin as they cycle. And that's going to use ATP. And then we're going to couple the action potential coming from the neuron and then traveling throughout the muscle plasma membrane, which is then going to cause an increase in calcium ions. And that in skeletal muscle, we're going to have an actin-based control system where we're going to have counseling binding troponin, which then moves tropomyosin on the actin. And then we're going to have removal of calcium through the actions of the SR calcium atpase.
