Welcome, so today we wanna continue our discussion of muscle. And in particularly we're gonna consider smooth muscle. Smooth muscle is an involuntary muscle. This is the muscle that makes up the walls of the organs, and it surrounds some of the blood vessels within your body. So the learning objective for today will be that we'll describe the structure and the function of the smooth muscle. We want to explain how the myofilaments are regulated to form force, or to provide contraction. And then we want to talk about the types of stimuli that activate smooth muscle. And explain how the spontaneous electrical activity can occur in some types of smooth muscle. And these are a special subclass of smooth muscle, which are called pacemakers. And last, we'll consider the two major classes of smooth muscle which are called single-unit and multi-unit. So there's quite a few things to deal with. So the first thing to think about is that smooth muscle, like other muscle, such as skeletal and cardiac, does follow the shared principles of muscle in general. And that is, that it uses the sliding filament mechanism and that the contractile filaments are myosin and actin. Myosin being the thick filament and actin the thin filament, and they will slide past one another to provide shortening. And that these interactions between the myocin and the actin will be controlled by calcium. And that the calcium will change within the interior of the cell. That is, we will increase calcium, or decrease calcium levels in response to stimuli. Now the smooth muscle fiber is a relatively small cell. This is a cell that's able to divide throughout the life of the body. And it will change in size in response to the type of workload that's being presented. For instance, in the non-pregnant uterus, the smooth muscle fibers are small. But that in the pregnant uterus, then they become much larger. The smooth muscle cell itself is a thin cell which is only about 2 to 20 micrometers in diameter, 2 to 20 micrometers in diameter. And that the cell is cigar shaped, and that's what's diagrammed here. And in the center of the cell, we have the nucleus. Because these cells are very thin, there are no T tubules to move the electrical activity into the interior of the cell. So, we have no T tubules, and in addition to that, the regulation of the myofibrils, the myofilaments, are going to be by calcium. But that will not be the regulation of actin, as we saw with skeletal muscle. And that is because there is no troponin-tropomyosin complex present on the actin filaments. The regulation will be by calcium, but we will regulate the thick filament. And by regulating the thick filament, then we can have cross-bridge formation. The other thing about the smooth muscle is that when you look at it by light microscopy the sarcomeres are not, that is the regular A-I banding that we saw in skeletal muscle, is not very apparent. And that's why it's called smooth muscle. And this is because the actin filaments are attached to the plasma membrane in dense bodies. And they're attached at an angle across the interior of the cell, so that the sarcomeres, then, do not align well within the cell, and we don't get that nice A-I banding. These dense bodies are analogous to the Z-lines that we saw within the skeletal muscle, and we will again see within cardiac muscle. Because of the arrangement of actin within these cells, that is it's at an angle to the surface of the cell, when you have contraction then the cell will shorten. And as the cell shortens, it forms more of a postage stamp shape. That is, it becomes more of a square, or cube shape, rather than this elongated cigar shape. Now the calcium, as I said, regulates the myosin filament. That is, the thick filament of the sarcomere. And the increase in intracellular calcium activates what's called the myosin light chain kinase. This is an enzyme, a kinase is an enzyme and a kinase always adds a phosphate group, phosphorylations, to its target. The myosin itself is a rod-like structure that has a head group, which looks like this. And the ATPase is part of that head group. So that's where the enzymatic activity of the myosin resides. But myosin, in addition to this heavy chain, myosin has this light chain, which is a regulatory chain. And this myosin light chain then will become phosphorylated in the presence of calcium, by this kinase. When that occurs, then that activates the myosin head. And now the myosin head can interact with actin and undergo the power stroke. And we will get then shortening, or a development of tension, within the cell. So it's the calcium then that's going to regulate the interaction of actin and myosin. But we're regulating the thick filament, not the thin filament, in this situation. Importantly, removal of calcium will allow the cell to relax. And the removal of calcium, once calcium levels fall, then we remove the phosphate group from the myosin light chain. And then the interaction between myosin and actin ends. The calcium that is used by these cells for contraction is able to enter the cells from the outside, or the ECF. So it's able to come in across the plasma membrane in sufficient amounts, so that you can then cause a contractions within the cell. There is also a sarcoplasmic reticulum which is present within these cells, which is again an intracellular calcium storage site. And that calcium is also released, and it adds to the calcium which is coming in from the exterior of the cell. Now smooth muscle has two very different types of contraction. The myosin that's on the smooth muscle is called a slow myosin. That is, it has a slow kinetics, so that's one way that it's different from skeletal muscle myosin. But in addition to that, when we activated skeletal muscle, what happened was that we got a contraction and that the entire cell was activated. In the case of smooth muscle, some of the smooth muscles had that same type of phasic contraction, and they're called phasic smooth muscle. So when you stimulate those cells, you will get a single contraction or a single twitch. And that will be followed, then, by relaxation. But there's also a smooth muscle, which is called a tonic smooth muscle. This smooth muscle is found In the muscle that surrounds blood vessels, for instance. So, in our very small arterials, we have smooth muscle around the lumen of the cells. And that smooth muscle can undergo different states of contraction and holds that for very long periods of time. So this then is the amount of tension that's developed by the smooth muscle, is going to be proportional to the stimulus that's given to that smooth muscle. And then it can hold it over time. So for instance, in your basal state, we could have a blood vessel that has a lumen that's of this diameter. When we cause the smooth muscle to contract, we can then make the diameter of the lumen much smaller. And we can hold that for long periods of time, or the smooth muscle can relax, and when the smooth muscle relaxes, we can have a much larger lumen to that blood vessel. And that again can be held for very long periods of time. So this then it's called the tonic control of blood vessels or tonic smooth muscle contraction. Smooth muscle also is very complicated in the way the contractal events are regulated. And that is that we have multiple ways that we can stimulate the cells. And that you can have both a positive input to the cells, as well as a negative input to the cells. And its the net input to the cells which governs whether or not the cell is going to contract or to relax. The first way that you can change the state of the cell is by simply a mechanically gated channels are activated. When we activate mechanically gated channels, we are stretching the walls of the smooth muscle. And by stretching the walls of the muscle then calcium can enter into the cells. And this occurs very frequently in blood vessels where you have a higher amount of blood being delivered to the particular vessel. The walls of the vessel stretch because of the increase in volume. And then, in response to that, calcium enters the cells and the muscles then contract and bring back to the original tonic state of contraction. The second way that we can control the relaxation and contraction state of the smooth muscle is through ligand gated channels or receptors. And this is predominantly modulated by the autonomic nervous system and that is by the neurotransmitter norepinephrine. Norepinephrine can work on two completely different types of receptors. For instance, we have an alpha-1 adrenergic receptor and the alpha-1 adrenergic receptors pressing on the blood vessels will cause contraction when activated. And then, the norepinephrine can also bind to, and this would be on blood vessels, but norepinephrine can also bind to a different type of adrenergic receptor which is called the beta-2 receptors. And the beta two adrenergic receptor are found in the lung on the bronchi of the lung, that is the airways, the larger airways of the lung. There the smooth muscle in response to norepinephrine the smooth muscle relaxes and does not contract. So you can have very different responses to the same neurotransmitter depending upon the receptor type. In addition, smooth muscle is sensitive to hormones such as oxytocin. Oxytocin is a hormone that, when secreted into the bloodstream of a pregnant female, will cause the smooth muscle of the uterus to contract. In addition, we can have smooth muscle being sensitive to paracrine agents or paracrine factors. For instance, potassium. So when you have a skeletal muscle that is exercising and is increasing the amount of potassium, which is outside of the skeletal muscle, that will cause blood vessels in that area to dilate. The smooth muscle in the walls of those blood vessels dilate and more blood, then, is delivered to the active muscle. So we have these local factors, then, which will govern the status of the smooth muscle. In addition to ligand-gated channels or receptors, we also have voltage-gated channels, and here these are the voltage-gated calcium channels. And this is very important, especially in the case of our pacemakers, which we'll talk about in just a few minutes. So under these conditions, the voltage changes across the plasma membrane, the channels are activated, and then calcium enters into the cells and causes contraction. Okay, so what about these pacemakers? So the pacemakers are an unusual type of muscle. And that is that they have unstable resting membrane potential. And that's what is diagrammed here. So the pacemaker potential can start at say -55 mV. And as you can see, the pacemaker potential slowly drifts up towards threshold. And once it reaches threshold, which could be at say -35 mV, then we have a very fast upward depolarization which occurs. As the cells are depolarizing, this is due to the opening of the voltage gated calcium channels. Calcium is entering the cells and the cells are rapidly depolarizing. Then the cells will repolarize and the repolarization is due to the entry of the potassium. And this is again opening of a voltage gated potassium channel. And by opening the voltage gated potassium channel, then the resting membrane potential or the membrane potential in these cells, then it starts to decrease and it goes back to its original -55 mV. When it reaches the -55 mV, many of these potassium channels, the voltage get a potassium channels, start to close and as they start to close then the cells will drift again back up towards the threshold. And when they hit threshold, then they will have again an opening of a voltage gated calcium channel and we repeat the cycle. The thing to notice about the pacemaker activity is that it is a timed event that occurs in a rhymetic manner. So there is always a periodicity to the pacemakers and the particular pacemaker has an intrinsic periodicity. These pacemakers are found within the smooth muscle of the GI tract. That is the gastrointestinal tract. They're found within the stomach, and they're found within the walls of the small intestine. And we'll talk about them when we talk about the gastrointestinal tract. Now the non-pacemaker smooth muscle can be divided into two categories. We have those which are called single unit smooth muscles, and this is where the cells are innervated. But there's only a few cells that are innervated, and all of the rest of the cells within the sheet of of smooth muscle will be connected through gap junctions. So we have electrical conduction, then through these gap junctions, where only a few cells are stimulated, but the entire sheath will respond. Because the calcium is then able to move from one cell to another through the gap junctions. And we get a synchronous contraction. Or we get a synchronous relaxation depending upon what our input. These types of smooth muscles are found within the gastrointestinal tract so that we have the walls of the tract then will contract and relax as a unit. They're found within the uterus and they're found within the small blood vessels such as the arterials. In contract to that we have multi-unit smooth muscle. The multi-unit smooth muscle simply is a cell which is not connected to it's neighbor through these gap junctions. But instead each cell is innervated or each cell will be stimulated. And under these conditions, then a stimulation of the muscle. Will cause a contraction but it's not an entire sheet that's going to respond. But just the single cell that will respond. This type of muscle is found associated with the hair on your arm. So that when you're cold, for instance, the hair rises. And that's due to the contraction of the smooth muscle. Which causes the hair to elevate. The thing about the smooth muscles in both of these conditions is that they will be either electrically coupled. As a single unit smooth muscle, or they'll not be electrically coupled. That is, they'll be no gap junctions within the multi-unit smooth muscle. But in both cases, they have a junctional area which is an adhesion junction. Through, which are called desmosomes. And that allows the cells to pull against one another. So that they, when they develop force they are pulling on their neighbors. Okay, so what's our key concepts, then? So the first is that the smooth muscle is an involuntary non striated muscle. It's associated with blood vessels and with the walls of the visceral organs. Secondly, the smooth muscle contains these overlapping protein myofilaments, and these are actin and myosin. And that it is the relative sliding of the actin and myosin past one another which gives us force generation. And also shortening of the cell. And this, of course, involves cross bridge formation between the actin and the myosin. And that's driven by the ATP, a activity of the myosin head. And that we said this is a slow myosin hit, so it's a slow enzymatic activity. The third is, is that the coupling between a membrane action potential and contraction is mediated. By calcium ions, just as we saw within skeletal muscle, and as we will see, within cardiac muscle. But here, the calcium regulates the myosin and that biphosphorolic calcium causes a phosphorylation of the myosin light chain. And that allows the myosin head then to interact with the actin. And this cross bridge formation then can lead to contraction. The fourth of our key concepts is that the smooth muscle can be regulated in multiple ways. That is it can be regulated by the autonomic nervous system. And that some smooth muscle is regulated by stretch. That is our mechano activated channels or by paracrine factors and hormones. So we can have both endocrine and paracrine local factors. Which can regulate the smooth muscles contraction state. The fifth is that in pacemaker cells, and not all smooth muscle is a pacemaker cell. But in those which are pacemaker cells the action potentials are initiated by an influx of extracellular calcium. And that the timing of the contractions, that is, that the timing of these cells. Generating an action potential, is rhythmic, and that you'll have a certain periodicity to the pacemaker. And six, some smooth muscle exhibits fused tension. And that is that our fasic muscle can contract and give us a fused tetanus. And we see this, for instance, at the sphincters which are between, which are located within different regions of the GI track. So between the esophagus and the stomach or between the stomach and the small intestine. There are sphincters and these sphincters are normally closed. That is they're under a, they are, fully contracted but that they can be relaxed by specific factors or inputs. Which allow materials to be moved from one region of the GI tract to the next. These are the phasic cells. The tonic contractions, then, are the cells which we find around the smooth muscle cells. Which we find around blood vessels, for instance, where they will contract. And then they can hold their state for very long periods of time. And actually, as I think about it, the sphincters are those which are for tonic contraction. So sphincters have tonic contraction. They can hold it for very long periods of time. Phasic would be smooth muscle that will contract rapidly and then relax rapidly. And they are not part of the sphincters. Sorry I misspoke about that. Okay, so I hope that you'll join us in the next time, see you then. Bye bye.
