Welcome. Today we're going to talk about the third type of muscle which is called cardiac muscle. This is a striated muscle but it is, it is innovated by the autonomic nervous system. It is an involuntary muscle. Cardiac muscle is a muscle that makes up the heart, the walls of the heart and it also makes up some of the walls of the pulmotic vein which is going to, coming from the lung. The cardiac muscle cell is, is in size it's between the skeletal muscle and the smooth muscle. Cardiac muscle cells have blunt ends and these blunt ends, so it looks like this. And these, and the cell itself has a central nucleus and the cell is about 25 microns in diameter. At the blunt ends we have mechanical coupling of the, of one cardiac muscle fiber to a second. And this is an area which is called the intercalated disc. This mechanical coupling is what's encompasses desmosomes. And a fascia adherence. So, this is simply allowing the, the muscles, then, to pull against one another when they're contracting. In addition, the cardiac muscle cells are in fact, electrically coupled and that's what's shown here. And this is on the sides of these muscles. And this is, this is where we have our gap junctions. So we have then both electrical coupling as well as mechanical coupling. So when these cells contract, they're going to contract then, as a sheet. We do see very prominent A and I banding and this is that, because the sarcomeres are very well aligned and a, along the linear array of the cell. So the striations then are due to the overlaps of actin and myosin, just as what we have in skeletal muscle. And then of course we have central nuclei and flanking the nuclei we can often see mitochondria, these cells are going to have a slow ATPase and they're going to be oxidative fibers. The excitation-contraction coupling is very similar to what we see in striated muscle in skeletal muscle. The action potentials will sweep along these cells and then enter into the T-tubules. And as the action, the depolarization enters into the T-tubules, we will then open the Dihydropyridine. In receptor. The dihydrapurity/g receptor in these cells is in fact a voltage gated calcium channel. So a very small amount of calcium will enter into the, into the sidisol/g and this is going to be called the trigger calcium. It's going to bind to the ryanodine receptors which are present on the sarcoplasmic reticulum in a close opposition to the dihyrodropyridine receptors. In cardiac muscle, these two components, that is the ryanodine channel and the dihydrop[INAUDIBLE] receptor are not physically connected, but they're in very close proximity, so that the little bit of trikle, or trigger calcium that enters into the cells then will bind to the[INAUDIBLE] And, and activate the ryanodine channel. When a, when calcium binds to the ryanodine receptor, then calcium is then going to exit from the sarcoplasmic reticulum. And again, sarcoplasmic reticulum in these cells is a membrane bound vesicle where it stores very, very high amounts of calcium. This calcium, now, is going to flood the entire cytoplasm and it's going to bind to the troponin which is present on. The, the thin filament of that is our actin. The Troponin-tropomyosin complex is then going to roll out of the groove and unmask actin, so that the head groups of myosin can now engage onto the actin, and pull the actin along, as it does in skeletal muscle. Muscle. As long as we have calcium present this, this event will occur and we will generate tension. Now, to remove the calcium then we have, tw-, three separate ways. The first is the sarcoplasmic reticulum has a calcium ATPA's which is pumping calcium back into the SR. The second is this that we have a sodium calcium exchanger where 3 sodiums are entering the cell for every calcium that's exiting the cell. And these are located on the plasma membranes of the cardiac myocyte. And thirdly we're have a calcium ATPase which is actually present on the plasma membrane of these cells and it is going to pump calcium out of the cell and into the ECF. So the ECF is here. The dominant factor in removing calcium from the cytoplasm, is in fact the sarcoplasmic reticulum, calcium ATPase. As long as calcium is present, we have contraction. And the contraction in the heart is going to be called systole. And once we remove the calcium, we'll have relaxation, and that's going to be caused, called diastole. And we return to these terms later, in fact, and the next time when we come in and we're talking about the heart Itself. Now the heart is actually made up of two parts of cardiac muscle fibers. One is the, the fiber that's actually going to general the tension. This is the one that's actually going to contract and give is and give us a squeeze. That is the actual squeezing of a, of the chamber of the heart. The second is an electrical conducting system. That only represents about 1% of the total cells which are within the heart. So, the majority of the cells that are within the heart are contractile fibers. The contractile fibers have what's called a fast-action potential. That's what we're going to look at here. So the, the action potential, then. The cells are going to start at a minus 85 millivolts. And that's their resting membrane potential. And when they receive a signal to contract, these are a sig-, and electrical signal to depolarize. The cells will open a voltage gated The sodium channel. These are the same voltage-gated sodium channels that we have in nerve and in skeletal muscle. Calcium enters the cells, and the cells rapidly depolarize. As the cells rapidly depolarize, these voltage-gated sodium channels will undergo inactivation. And as they undergo inactivation, so these are going to be inactivating. Then at the same time, we're going to open the voltage gated potassium channels. So we have then what's known as a slight notch. The slight notch is where we're having a slight depolarization of the cells. We've closing the voltage gated sodium. Not closing them but inactivating them and we are opening the voltage gated potassium. We then have following that, we then have a, a period of time where we have a plateau and that is, is if the electrical con, the resting membrane, the membrane potential is now almost flat. This is a period where we have influx of calcium. We are opening the calcium l type channels. These are again voltage gated channels. And we still have the voltage gated potassium channels open. And so the in, the entry of calcium is being balanced by the exit of potassium from the cells. And that's giving us almost a, an equal In, in equilibrium in our potential. And then, then this is followed by the actual re-polarization event, and this is where our calcium L-type channels close, and we have potassium, the voltage-gated potassium channels are still open. And so the cells then are going to go back to the resting membrane potential. So, this is the re-polarization event. And at the resting number in potential, we have our sodium potassium ATPase that, that brings us back to our beginning state. This fast action potential is, has said to have phases. And phase zero is going to be where we open, or have our initial de-polarization and we're opening those voltage-gated sodium channels. Phase one is where we have the notch and that is to set those sodium channels are inactivating and we're opening the potassium channels. In phase two or our plateau phase is where we have calcium entering the cells and we have potassium exiting the cells. And then in phase three we're going to have repolarization. And that's when we only have potassium, voltage-gated potassium open, and the cells are now repolarizing. Excuse me. And in phase four, we're then back to our resting membrane potential. Now, notice that this action potential is actually quite long in duration. The action potential is about 200 milliseconds. And this is in comparison to what we saw with the action potential of neurons, which was one millisecond, and the action potential for skeletal muscle, which is between two and five milliseconds. So, the action potential then for the heart, or for the caridac muscle is. Of the fast action potentials is very, very long. Now because the action potential is very long, what we. It, it actually has a very important property then. It gives a very important property to the cardiac muscle ce, cell. This long period of, of, of the action potential means that up to the was from zero to 200 miliseconds. Those, those sodium channels are going to be in an inactive state. So we're going to have sodium channels which are in an inactive state. And that means that if we try to, to give a stimulus to the cells at this at this time, that the cells actually cannot Then undergo a second action potential. The consequence of this is that you cannot get summation of your action potentials, so that we're, we're always going to have htis 200 millisecond duraiton between. This is true, this is called the refractory period where those voltage gated sodium channels are inactive. And the, and the absolute refractory period actually is between zero and about 180 milliseconds. So under those conditions we, when we stimulate we can not get another action potential. But between 180 and 200 milliseconds, if you get a big enough stimulus, you can in fact, start another action potential. Because enough of those voltage gated sodium channels now have moved from the inactive state To the closed state. And they can then be reopened. And that's, then, going to be called the relative refractory period. So when you have an absolute refractory period, from 0 to 180 milliseconds. And a relative refractory period from 180 to 200. Hundred milliseconds. Now in addition to having a very long action potential, we, our twitch is also going to be much longer than what we see in skeletal muscle. In skeletal muscle, the twitch is going to be from about 20 up to 100 milliseconds. So we have a, a, an action potential that is 2 to 5 milliseconds, and the twitch from 20 to 100 milliseconds. In the cardiac muscle we have an action potential that's 200 milliseconds, and the twitch is 250. So that the, that the twitch then, that is a single contractible event, is going to be equal to 250 milliseconds, and our action potential Is 200 milliseconds. If I stimulate them I cannot summate those twitches. So that, so that means that I can never get to a summed a summed state where we would have fused tetany. And this is actually a good idea for the heart, in the sense that if the heart went into tetanus then we would be able to fill the heart with blood. So this, so under these conditions then, the cardiac myocin's are not able to undergo summated contractions and, And to give us tetanus. This one other aspect about the heart which is different from skeletal muscle. In skeletal muscle, when we contract the skeletal muscle, the entire fiber is going to contract. In the heart, when we activate the heart, the cardiac[UNKNOWN] are also going to contract and they're going to give us the maximal tension. So they don't have a graded contraction state like we saw with smooth muscle. They're going to give us one large contraction and they're going to contract as a unit so that all of the fibers within the heart are going to be connected through these electrical, electrical junctions these gap junctions and so we're going to contract as a sheet. This simply means that there is no way that the heart is able to recruit more fibers to get a th, get a stronger contractal event. A stronger contraction. The skeletal muscle, we can, we have recruitment of fibers until we get the maximal amount of tension out of a, a given Muscle. But in cardiac, you can't do that. So the cardiac muscle fibers are actually changed by the body in such a way that they're sort of tweaked by the body to give a little bit extra contract attention. And one of the ways that it does this is that, it's in filling. That is, in the actual stretch of the myosite, and that's what's shown here. So, the tension, which is going to be developed versus the length of the actual fiber or the sarcomere length. And what we see is that the cardiac muscle. Is that, we can have an optimal range, where the sarcomeres are going to have an overlap which is going to give us maximal tension. If we have no overlap. Obviously, we have less tension. And if the, if the cells are actually. Contracted down too far then, again, we're going to not be able to get enough tension. In the cardiac, in the heart, what happens is that this, the resting state, that is in diastole, the heart is sitting at a sub-optimal length. And that, with filling the heart, we stretch the fibers. And by stretching the fibers we move to the optimal range for the Sarcomere length. This is called the Frank Starling law of the heart. And it's the, one of the main reasons that they think that the tension will increase when you stretch the, the fibers. It's still a controversial subject because other things can be occurring within the sarcomeres themselves, which are giving us better tension. But at this point, this is one of the, the major or most prevalent. So the heart, the heart then is going to give us a stronger contraction, as we fill the heart and stretch the fibers. So what are our key concepts? So the first is that the cardiac muscle fiber is an involuntary, and it's a striped a striated. The type of muscle. Secondly the cardiac mya, muscle, contains these overlapping protein myofilaments, which is actin and myosin. And there, there interaction, there sliding past one and other, is going to generate a force. And this process then is going to cause is going to involve cross bridge formation between the actin and the myosin. And it's driven by the ATP, which is the energy source which is being used by the myosin ATPase. The cardiac muscle fibers are going to have a slow action potential. They're, they have a slow ATPase on their myosin heads, and they're an oxidated fiber. Third, we have coupling between our membrane action potentials and the contraction. And this is mediated by calcium ions. And in cardiac muscle, calcium regulates the actin, that is the thin filament, again through troponin, by binding to troponin, which then changes the troponin tropomyosin complex, and unmasks actin. Fourth, we have autonomic nervous system is going to regulate the cardiac muscle. Five, the action potentials are going to be initiated by influx of extracellular sodium, and these are the same voltage gated sodium channels that we saw in nerve and in skeletal muscle. In six, the cardiac muscle is going to contract in unison and the, and, and because it contracts in unison it can contract in unison because it is coupled through these electrical junctions, which are the gap junctions. The cardiac muscle does not develop fused tetanus and the reason for this is because the action potential and the twitch duration is almost the same length. So next time we come in, then we're going to start talking about the cardiovascular system and actually how the, this muscle then is working within the heart to, to generate force and to allow the heart to, to act as a pump. See you next time.
