 This video is part 2 of muscle physiology, covering the objective, compare skeletal muscle and cardiac muscle based on their innervation, structure, and contraction mechanisms. In the last video I discussed how auto-rhythmic cells stimulate contraction of the heart through an intrinsic excitation mechanism where the auto-rhythmic cells are spontaneously depolarized, producing an action potential that spreads through the cardiac muscle tissue. Stimulating an action potential in the contractile cells, here we see a graph of the contractile cell action potential. When the membrane is depolarized to threshold for opening of voltage gated sodium channels, sodium influx causes rapid depolarization during the rising phase of the contractile cell action potential shown in the orange line. As voltage gated sodium channels become inactivated, L-type calcium channels open and voltage gated potassium channels open. This causes the plateau phase of the contractile cell action potential because the positive charges that flow into the cell through the L-type calcium channel are balanced by the positive charges that flow out of the cell through the voltage gated potassium channel. This plateau phase also corresponds to the absolute refractory period. Once the L-type calcium channels close, the flow of potassium through voltage gated potassium channels enables repolarization during the falling phase of the contractile cell action potential shown with the blue line. During the plateau phase of the contractile cell action potential, calcium rushes into the cytosol from the extracellular fluid through L-type calcium channels while calcium is entering the cell from the extracellular fluid through the L-type calcium channels. There's also calcium being released from inside the sarcoplasmic reticulum through rhanodine receptors. Rhanodine receptors are activated through a mechanism known as calcium induced calcium release. This is where calcium flowing in from the extracellular fluid through the L-type calcium channel activates opening of the rhanodine receptor, which is another calcium channel, but the rhanodine receptor allows calcium to flow into the cytosol from the sarcoplasmic reticulum. Cardiac muscle is striated like skeletal muscle, resulting from the overlapping thick and thin filaments organized into sarcomeres. While the thick filaments contain the motor protein myosin, thin filaments contain actin, tropomyosin, and troponin. Tropomyosin covers the binding site for myosin on actin when the muscle fiber is at rest. Troponin is the calcium sensor protein that causes tropomyosin to move off of the binding site for myosin of actin. This will allow myosin to bind to actin in the first step of the power stroke cycle in the sliding filament theory cross bridge formation. Here we see an illustration of the sliding filament theory of contraction, which is the same basic mechanism of contraction in cardiac muscle as we saw for skeletal muscle. It has the four steps of the power stroke cycle, starting with cross bridge formation, followed by the second step, the working stroke or power stroke, where the myosin head pivots pulling on actin. The third step is cross bridge detachment, which is stimulated when ATP binds to myosin. And the final step in the power stroke cycle of the sliding filament theory is cocking of the myosin head. As myosin catalyzes hydrolysis of ATP, the energy released is used to move myosin into the high energy conformation, preparing for another round of the power stroke cycle. Here we see a comparison of the time course of the action potential and contraction in skeletal muscle versus cardiac muscle. In skeletal muscle, the action potential lasts about two milliseconds, and the duration of a twitch is around 50 milliseconds. Therefore, we can have a high frequency of action potentials, stimulating summation of twitches. However, in cardiac muscle, the action potential duration is much longer, around 200 milliseconds, and this prevents summation. The absolute refractory period of the contractile cell action potential occurs for a long period of time throughout the plateau phase of the contractile cell action potential, preventing another action potential from occurring while the cardiac muscle is contracted. And this will allow time for the heart to relax before another action potential stimulates contraction. Cardiac muscle is innervated by the autonomic nervous system. In contrast, we saw skeletal muscle is innervated by the somatic efferent neurons, allowing us to have voluntary control over skeletal muscle. And those somatic efferent fibers released acetylcholine in order to excite the skeletal muscle contraction. In contrast, we saw that cardiac muscle is excited by an intrinsic mechanism where the auto-rhythmic cells spontaneously depolarize producing the action potential. However, cardiac muscle can be regulated by the autonomic nervous system, where the parasympathetic division of the autonomic nervous system will lead to a decrease in heart rate. The sympathetic division of the autonomic nervous system will stimulate an increase in heart rate and an increase in the force of contraction. Postganglionic parasympathetic fibers release the neurotransmitter acetylcholine in the SA node and AV node to decrease the heart rate. Postganglionic sympathetic fibers release the neurotransmitter norepinephrine in the SA node, the AV node, and throughout the myocardium of the heart in order to stimulate an increase in heart rate and an increase in the force of contraction. Here we see the mechanism through which the sympathetic nervous system stimulates an increase in heart rate by activating HCN channels. Norepinephrine released by postganglionic sympathetic fibers binds to beta-adrenergic receptors in the SA node and the beta-adrenergic receptor is activated, stimulating the G-protein that activates adenovil cyclase. The enzyme adenovil cyclase then produces the second messenger cyclic AMP and cyclic AMP binds to activating HCN channels so that more sodium will enter the cell during the pacemaker potential, leading to an increased slope of the pacemaker potential, which causes the membrane potential to reach threshold faster, stimulating an increased heart rate. Here we see the mechanism through which sympathetic activity increases contractility or the force of contraction in the heart by stimulating opening of L-type calcium channels. Norepinephrine released by postganglionic sympathetic fibers binds to beta-adrenergic receptors on the contractile cells in the myocardium. The beta-adrenergic receptor stimulates activation of adenovil cyclase to produce the second messenger cyclic AMP and cyclic AMP binds to and activates protein kinase A. Then protein kinase A phosphorylates L-type calcium channels and phosphorylation by protein kinase A stimulates opening of L-type calcium channels so more calcium will enter the cell during the plateau phase of the contractile cell action potential. Here we see the mechanism through which sympathetic activity stimulates an increased release of calcium from the sarcoplasmic reticulum. Again, the norepinephrine released by postganglionic sympathetic fibers is activating beta-adrenergic receptors on the surface of contractile cells, and this leads to the production of cyclic AMP, activating protein kinase A, and protein kinase A phosphorylates ranitine receptors. This stimulates opening of ranitine receptors, making the calcium-induced calcium release mechanism more sensitive, so more calcium will be released from the sarcoplasmic reticulum during the action potential. And this leads to an increased contractility, increasing the force of contraction. Here we see comparison of the contractile cell action potential at rest versus with sympathetic nervous system stimulation. We can see that the slope of the pacemaker potential or pre-potential spontaneous depolarization is increased, causing the membrane potential to reach threshold more quickly, stimulating an increase in the heart rate. Otto Loewe was awarded the Nobel Prize in Physiology or Medicine in 1936 for his discovery of the neurotransmitter acetylcholine. His research was investigating the effects of the vegas nerve, the tenth cranial nerve on the heart rate. The vegas nerve carries the pre-ganglionic parasympathetic efferent fibers that are regulating the heart. Here we see the mechanism through which the neurotransmitter acetylcholine stimulates a decrease in heart rate by activating potassium channels. Acetylcholine released from post-ganglionic parasympathetic fibers binds to the M2 muscarinic acetylcholine receptor, leading to activation of a G protein. The beta-gamma subunit of the G protein then binds to and activates a potassium channel. As potassium is flowing out of the cell, this causes a decrease in the slope of the pacemaker potential, contributing to a decrease in the heart rate. Here we see another mechanism leading to a decrease in heart rate following activation of the muscarinic acetylcholine receptors on the auto-rhythmic cells of the heart. The muscarinic acetylcholine receptor activates the alpha-G protein subunit, which inhibits the enzyme adenylyl cyclase, leading to decreased cyclic AMP with less cyclic AMP available to bind to the HCN channel. There's decreased sodium influx during the pacemaker potential of the auto-rhythmic cell action potential, therefore it takes longer to reach threshold and the heart rate decreases. So here we can see a comparison of the auto-rhythmic cell action potential at rest versus with parasympathetic stimulation. The acetylcholine released from post-ganglionic parasympathetic fibers stimulates opening of potassium channels and inhibits the opening of HCN channels, which causes a slower rate of depolarization during the pacemaker potential. This decreased slope of the pacemaker potential means that it takes longer for the membrane potential to reach threshold, therefore action potentials are generated at a lower frequency leading to a decrease in the heart rate.