Welcome, so today we want to continue our discussion of muscle. In particular, we will 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. The learning objective for today is to describe the structure and the function of the smooth muscle. We want to explain how the myofilaments are regulated to generate force and/ or to enable contraction. Then we want to consider the types of stimuli that activate smooth muscle and explain how the spontaneous electrical activity can occur in some types of smooth muscle. These cells are a special subclass of smooth muscle called pacemakers. And last, we'll consider the two major classes of smooth muscle which are called single-unit and multi-unit. 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, follows the shared principles of muscle in general. That is it uses the sliding filament mechanism. The contractile filaments are myosin and actin. Myosin is the thick filament and actin is the thin filament. These filaments slide past one another to provide shortening. The interactions between myosin and actin will be controlled by calcium. The calcium changes 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. 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, they become much larger. The smooth muscle cell itself is a thin cell only about 2 to 20 micrometers in diameter, 2 to 20 micrometers in diameter. The cell is cigar shaped. That is what is diagrammed here. In the center of the cell, is the nucleus. Because these cells are very thin, there are no T tubules to bring electrical activity into the interior of the cell. So, we have no T tubules. In addition to that, the regulation of the myofibrils, the myofilaments, is by calcium, but that Calcium will not regulate actin, as we saw with skeletal muscle. That is because there is no troponin-tropomyosin complex present on the actin filaments. The regulation is by calcium, but we will regulate the thick filament. By regulating the thick filament, 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 obvious. The regular A-I banding that we saw in skeletal muscle is not apparent. That's why it is called smooth muscle. The reason is that 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 the sarcomeres, then, do not align well within the cell. We don't observe that nice A-I banding. The 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 iss at an angle to the surface of the cell, contraction causes the cell to shorten. As the cell shortens, it forms more of a postage stamp shape. It becomes more of a square, or cube shape, rather than this elongated cigar shape. Now calcium, as I said, regulates the myosin filament. That is thick filament of the sarcomere. The increase in intracellular calcium activates what's called the myosin light chain kinase. This is an enzyme. A kinase is an enzyme. A kinase always adds a phosphate group, phosphorylates, its target. The myosin itself is a rod-like structure that has a head group, which looks like this. The ATPase is part of that head group. That's where the enzymatic activity of the myosin resides. But myosin, in addition to this heavy chain, has this light chain, which is a regulatory chain. 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. Now the myosin head can interact with actin and undergo the power stroke. We will get then shortening, or a development of tension, within the cell. It's the calcium that regulates 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. With the removal of calcium, once calcium levels fall, then we remove the phosphate group from the myosin light chain. 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, from the ECF. It is able to cross the plasma membrane in sufficient amounts to cause a contractions within the cell. There is also a sarcoplasmic reticulum present within these cells. This is again an intracellular calcium storage site. That calcium is also released. It adds to the calcium 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. It has only a slow kinetics. That is one way that it differs from skeletal muscle myosin. In addition to that, when we activated skeletal muscle, it contracted; the entire cell was activated. In the case of smooth muscle, some of smooth muscles have that same type of phasic contraction. They're called phasic smooth muscle. When you stimulate those cells, you will get a single contraction or a single twitch. That will be followed, then, by relaxation. But there's also a smooth muscle, called a tonic smooth muscle. This smooth muscle is found In the muscle that surrounds blood vessels. For instance in our very small arterioles, we have smooth muscle around the lumen of the cells. That smooth muscle can undergo different states of contraction and holds that contraction for very long periods of time. This means the amount of tension that's developed by the smooth muscle is proportional to the stimulus that's given to that smooth muscle. And that it can hold it over time. 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. We can hold that for long periods of time, or the smooth muscle can relax. When the smooth muscle relaxes, then we can have a much larger lumen to that blood vessel. Again that state can be held for very long periods of time. This then it is called tonic control of blood vessels or tonic smooth muscle contraction. Smooth muscle also is very complicated in the way the contraction events are regulated. There are multiple ways that we can stimulate the cells. You can have both a positive input to the cells, as well as a negative input to the cells. It is the net input to the cells which governs whether or not the cell either contracts or relaxes. The first way that you can change the state of the cell is by activating mechanically gated channels. When we activate mechanically gated channels, we are stretching the walls of the smooth muscle. By stretching the walls of the muscle then calcium can enter into the cells. 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 blood volume. Then, in response to that stretch, calcium enters the cells. The muscles contracts to return 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. This is by the neurotransmitter norepinephrine. Norepinephrine can work on two completely different types of receptors. For instance, we have an alpha-1 adrenergic receptor. The alpha-1 adrenergic receptors present on the blood vessels will cause contraction when activated. Norepinephrine then binds to receptors on blood vessels. Norepinephrine can also bind to a different type of adrenergic receptor called the beta-2 receptors. The beta 2 adrenergic receptors are found in the lung on the bronchi of the lung, that is the airways. The larger airways of the lung. There in response to norepinephrine, the smooth muscle relaxes. It 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, causes the smooth muscle of the uterus to contract. In addition, we can have smooth muscle sensitive to paracrine agents or paracrine factors. For instance, potassium. When a skeletal muscle is exercising, there is an increase in the amount of potassium, outside of the skeletal muscle. That rise in K+ will cause blood vessels in that area to dilate. The smooth muscle in the walls of those blood vessels relax and more blood, then is delivered to the active muscle. So we have these local factors, which will govern the status of the smooth muscle. In addition to ligand-gated channels or receptors, we also have voltage-gated channels. These are the voltage-gated calcium channels. This is very important, especially in the case of our pacemakers, which we'll talk about in just a few minutes. Under conditions where there is a voltage change across the plasma membrane, the calcium channels are activated. Calcium enters into the cells and causes contraction. Okay, so what about these pacemakers? The pacemakers are an unusual type of muscle. That is, they have an unstable resting membrane potential. That is what is diagrammed here. The pacemaker potential can start at say -55 mV. As you can see, the pacemaker potential slowly drifts up towards threshold. Once it reaches threshold, which could be at say -35 mV, then we have a very fast upward depolarization. The cells are depolarizing due to the opening of the voltage gated calcium channels. Calcium is entering the cells. The cells are rapidly depolarizing. Then the cells repolarize. Repolarization is due to the entry of the potassium. This is opening of a voltage gated potassium channel. By opening the voltage gated potassium channel, then the resting membrane potential or the membrane potential in these cells, starts to decrease. It returns to its original -55 mV. When it reaches the -55 mV, many of these potassium channels, the voltage gated potassium channels, start to close. As they close then the cells will drift again back up towards threshold. When the cell reaches threshold, then opening of a voltage gated calcium channels occur. We repeat the cycle. The thing to notice about the pacemaker activity is that it is a timed event that occurs in a rhythmic manner. There is always a periodicity to the pacemakers. 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. 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. This is where the cells are innervated. But only a few cells are innervated. All of the rest of the cells within the sheet of of smooth muscle are connected through gap junctions. So we have electrical conduction, through gap junctions. Only a few cells are stimulated, but the entire sheath will respond because calcium moves from one cell to another through the gap junctions. We get a synchronous contraction. Or we get a synchronous relaxation depending upon the input. These types of smooth muscles are found within the gastrointestinal tract. There the walls of the tract will contract and relax as a unit. They are found within the uterus and they're found within the small blood vessels such as the arterioles. In contrast, we have multi-unit smooth muscle. The multi-unit smooth muscle simply is a cell which is not connected to it's neighbor through gap junctions. Instead each cell is innervated. Each cell will be stimulated. Under these conditions, then stimulation of the muscle will cause a contraction but it's not an entire sheet that's going to respond. Just the single cell that will respond. This type of muscle is found associated with the hair on your arm. When you're cold, for instance, the hair rises. That's due to the contraction of the smooth muscle.It causes the hair to elevate. The thing about the smooth muscles in both of these conditions is that they are electrically coupled as a single unit smooth muscle, or not electrically coupled, That is there are no gap junctions within the multi-unit smooth muscle. In both cases, they have a junctional area which is an adhesion junction. These are called desmosomes. The desmosomes allow the cells to pull against one another. When they develop force, they are pulling on their neighbors. Okay, so what's our key concepts? 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, actin and myosin. It is the relative sliding of the actin and myosin past one another which gives us force generation and also shortening of the cell. This, of course, involves cross bridge formation between the actin and the myosin. That is driven by the ATP, the activity of the myosin head. We said this is a slow myosin head, so it's a slow enzymatic activity. Third 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, calcium regulates the myosin. Calcium causes phosphorylation of the myosin light chain. That allows the myosin head then to interact with the actin. This cross bridge formation can lead to contraction. The fourth of our key concepts is that the smooth muscle can be regulated in multiple ways. It can be regulated by the autonomic nervous system. 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 those which are pacemaker cells have the action potentials initiated by an influx of extracellular calcium. The timing of the contractions, that is the timing of these cells to generating an action potential, is rhythmic. There is a certain periodicity to the pacemaker. And six, some smooth muscle exhibits fused tension. And that is that our phasic muscle. It can contract to a fused tetanus. We see this, for instance, at the sphincters which are located within different regions of the GI tract. Between the esophagus and the stomach or between the stomach and the small intestine, there are sphincters. These sphincters are normally closed. That is they're fully contracted. But they can be relaxed by specific factors or inputs which allows materials to move from one region of the GI tract to the next. These are the phasic cells that generate tonic contractions. There other the cells, smooth muscle cells. Which we find around blood vessels. These can contract and then they can hold their state for very long periods of time. 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. They are not part of the sphincters. Sorry I misspoke about that. Okay, so I hope that you'll join us next time. See you then. Bye bye.