 This video will cover the following objective from muscle physiology. Compare skeletal muscle and smooth muscle based on their innervation, structure and contraction mechanism. Describe the characteristics of single unit and multi unit smooth muscles. Smooth muscles are found in the walls of hollow organs with the exception of the heart where cardiac muscle is found. Smooth muscle fibers are spindle shaped cells and they do not have striations. The innervation of smooth muscle is by autonomic efferent fibers in contrast to skeletal muscle that we saw is innervated by somatic efferent fibers. The autonomic efferent fibers have bulbous swellings called varicocities where neurotransmitters are released. These varicocities are swellings all along the length of the axon in contrast to axon terminals that are found only at the end of the axon. Smooth muscles are not striated, that is they do not have the alternating dark and light bands that we see in skeletal muscle. However, there are still myosin and actin proteins found inside smooth muscle fibers. The actin proteins are anchored to dense bodies. These dense bodies then are attached to the sarcolemma all around the smooth muscle fiber. When myosin is activated to produce contraction myosin still pulls on actin and this causes the dense bodies to be pulled closer to each other. As contraction proceeds the smooth muscle fiber will contract and decrease in volume as the myosin and actin are arranged between dense bodies diagonally around the cell the contraction will cause the smooth muscle to decrease in volume as it twists in a corkscrew like manner. Another important difference between smooth muscle and skeletal muscle is that smooth muscle does not contain the calcium sensor protein troponin. So if there is no troponin in smooth muscle how is excitation contraction coupling going to work? How can we stimulate contraction of smooth muscle fibers without troponin? In smooth muscle fibers there is a different calcium sensor protein known as calmodulin. When calcium binds to calmodulin the calcium calmodulin becomes activated and then calcium calmodulin complex binds to and activates an enzyme known as myosin light chain kinase. Myosin light chain kinase is going to become activated by calcium calmodulin and then myosin light chain kinase will phosphorylate myosin light chain in order to activate myosin. Here we see the activation of myosin light chain by phosphorylation. As myosin light chain kinase is activated by calcium calmodulin myosin light chain kinase then phosphorylates myosin light chain of the myosin protein inside of smooth muscles. This phosphorylation activates myosin. Following activation myosin will perform the four steps of the power stroke cycle in the sliding filament theory just like we saw in skeletal muscle fibers. The first step of the power stroke cycle in the sliding filament theory is cross bridge formation when myosin binds to actin. This is the same basic step however it's going to be stimulated when calcium binds to calmodulin and then calmodulin activates myosin light chain kinase. Myosin light chain kinase will phosphorylate myosin in order to stimulate cross bridge formation. So troponin is not found inside skeletal muscles but now the second step of the power stroke cycle is the working or power stroke where the myosin head pivots pulling on actin and this is the same basic step that we saw in skeletal muscles. In the next step of the power stroke cycle in the sliding filament theory ATP binds to myosin and stimulates cross bridge detachment then myosin performs hydrolysis of ATP and the energy released is used for cocking the myosin head in order to return to the high energy conformation where we started at the first step of the cross bridge. There are two different types of smooth muscle tissues. In single unit smooth muscle the autonomic neurons form synapses with only some of the smooth muscle fibers in the tissue and smooth muscle fibers are connected in a single unit smooth muscle tissue by gap junctions. These gap junctions allow ions such as calcium to flow from the cytosol of one cell into the cytosol of an adjacent cell. So as a single unit smooth muscle becomes excited that process of excitation will spread from one cell to the next cell through the tissue enabling the entire tissue to contract as a single unit hence the name. In contrast multi unit smooth muscle cells have autonomic neurons forming synapses with each of the muscle fibers. This enables the autonomic nervous system to control smooth muscle fibers individually within a multi unit smooth muscle tissue. You can see in the illustration here multi unit smooth muscles are found in the ciliary bodies within the eye so all of the intraocular muscles of the eye are multi unit smooth muscle including the ciliary muscles that control the shape of the lens in order to allow near point accommodation these muscles contract leading to increase curvature of the lens and increase bending of light to help us focus on an object close to our face. The smooth muscle of the iris that controls the diameter of the pupil is also an example of multi unit smooth muscle. Single unit smooth muscle can be found lining hollow organs such as the stomach and the intestines. There's also single unit smooth muscle in the uterus forming the myometrium the muscle layer of the uterus there's smooth muscle forming the lining of the urinary bladder and that's also a form of single unit smooth muscle lining the urinary bladder. Single unit smooth muscle is excited by cells known as interstitial cells of cahal. The interstitial cells of cahal perform an autonomous excitation mechanism meaning that excitation is generated from within the smooth muscle tissue. These interstitial cells of cahal function as pacemaker cells or pace setter cells that is these cells stimulate an action potential that will then spread through the single unit smooth muscle tissue. Then as that action potential spreads through the smooth muscle fibers the action potential will trigger opening of calcium channels known as L type calcium channels. L type calcium channels are voltage gated calcium channels that stay open for a long time after activation by the action potential. So these ion channels will stay open for 100 to 200 milliseconds allowing calcium to rush into the smooth muscle fibers and then calcium will bind to calmodulin stimulating myosin light chain kinase to phosphorylate myosin light chain activating the contraction mechanism. Interstitial cells of cahal are named after the famous neuroanatomist Santiago Ramani cahal that discovered them. Cahal along with another neuroanatomist Camilo Golgi received the Nobel Prize in Physiology or Medicine in 1906 for their work where they essentially were the first neuroanatomists to make detailed drawings of the structure of the nervous system. In the upper right here we can see an illustration of the interstitial cells of cahal, an illustration that was drawn from the histology of the smooth muscle in the intestines. So the interstitial cells of cahal can be seen in the picture in the top right here as the darker staining cells. So interstitial cells of cahal are adjacent to and just outside of the smooth muscle fibers that perform contraction inside of the single unit smooth muscle tissue. But the interstitial cells, they have a spontaneous change in their membrane potential that will then spread through the single unit smooth muscle tissue. This spontaneous change in the membrane potential is known as the slow wave. As the slow wave spreads into smooth muscle it will trigger opening of voltage gated channels causing an action potential and calcium will rush into the cell during the action potential to stimulate contraction. As the depolarization is produced that is what stimulates contraction but the intensity of contraction can be regulated by increasing the amount of action potentials, increasing the amount of calcium that enters the cell during each action potential. Here we see the L-type calcium channel that becomes activated in response to an action potential. When the depolarization triggers opening of the L-type voltage gated calcium channel, calcium rushes from the extracellular fluid into the cytosol of the smooth muscle cell. Then calcium binds to chalmodulin activating myosin light chain kinase to phosphorylate myosin light chain leading to activation of myosin enabling cross bridge formation. Following cross bridge formation we will have the working stroke then cross bridge detachment and then cocking of the myosin head and this working stroke will repeat over and over again as we go through the four steps of the power stroke cycle in the sliding filament theory. Smooth muscle is regulated by the autonomic nervous system. Here we can see an example of how the parasympathetic nervous system can stimulate the multi unit smooth muscle of the iris leading to constriction of the pupil. Post ganglionic parasympathetic neurons release acetylcholine into the iris onto the circularly arranged pupillary constrictor muscles. Acetylcholine binds to M3 muscarinic acetylcholine receptors on the surface of the pupillary constrictor muscles. The muscarinic receptor is a heterotrimeric G protein coupled receptor and the G protein that becomes activated will then activate an enzyme called phospholipase C. Now phospholipase C will stimulate the production of a second messenger known as inositol triphosphate and then inositol triphosphate will stimulate the release of calcium inside of the cell in order to stimulate contraction. And as the pupillary constrictor smooth muscles contract the diameter of the pupil will decrease. Here we see an example of how the sympathetic nervous system can stimulate contraction of multi unit smooth muscle in the iris. The radially arranged pupillary dilator smooth muscles are stimulated by the sympathetic nervous system. Post ganglionic sympathetic neurons release the neurotransmitter norepinephrine to stimulate contraction of the pupillary dilator muscles. Norepinephrine binds to an alpha adrenergic receptor which is a heterotrimeric G protein coupled receptor. The G protein of this receptor then activates the enzyme phospholipase C and phospholipase C will produce a second messenger known as inositol triphosphate which stimulates the release of calcium leading to smooth muscle contraction in the pupillary dilator muscles. Causing increased diameter of the pupil to increase the amount of light entering the eye. Here we see another example of how the sympathetic nervous system can stimulate contraction of smooth muscle. This example is the smooth muscle in the walls of our blood vessels. When post ganglionic sympathetic fibers release norepinephrine into the muscular layer of the blood vessel, norepinephrine binds to alpha adrenergic receptors on the smooth muscle cells. The alpha adrenergic receptor then activates a G protein which will then activate phospholipase C and then phospholipase C is an enzyme that will produce the second messenger IP3 or inositol triphosphate leading to increased calcium release from the endoplasmic reticulum. And that calcium will then stimulate contraction and in our blood vessels contraction of the smooth muscle causes something known as vasoconstriction. So vasoconstriction is contraction of smooth muscle in the wall of a blood vessel leading to a decrease in diameter which will make it more difficult for blood to flow through that blood vessel. It increases the resistance to blood flow and this is important to regulate blood flow and blood pressure. Here we see the function of the enzyme phospholipase C which becomes activated in order to stimulate smooth muscle contraction. Phospholipase C takes the substrate phosphatidyl inositol diphosphate which is a phospholipid in the plasma membrane and phospholipase C catalyzes hydrolysis of phosphatidyl inositol diphosphate producing diacylglycerol and inositol triphosphate. Inositol triphosphate then is the second messenger molecule that will stimulate the release of calcium inside of smooth muscle cells. Inositol triphosphate binds to a protein known as the inositol triphosphate receptor or IP3 receptor which is in the membrane of the sarcoplasmic reticulum. The IP3 receptor functions as a calcium channel. When IP3 binds to the IP3 receptor it stimulates opening of the calcium channel to allow calcium to exit the sarcoplasmic reticulum and enter the cytosol of the smooth muscle cell. This increases the calcium concentration of the smooth muscle cell and then calcium will activate chalmodulin leading to activation of myosinlight chain kinase. Here we see the mechanism where the adrenergic receptor activates phospholipase C leading to the production of inositol triphosphate and inositol triphosphate binds to the IP3 receptor in the membrane of the sarcoplasmic reticulum, activating opening of the calcium channel so that calcium can flow from the sarcoplasmic reticulum into the cytosol of the smooth muscle fiber. Calcium then binds to chalmodulin in the cytoplasm, activating chalmodulin to stimulate myosinlight chain kinase, then myosinlight chain kinase phosphorylates myosin, activating myosin to enable contraction.