CV System and Heart As A Pump

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CV System and Heart As A Pump

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University of Southern California
Bisc 307l - General Physiology
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BISC 307L 2nd Edition Lecture 26 Current Lecture Sympathetic Stimulation Increases Heart Rate Sympathetic transmitters(epi) raise heart rate, and parasympathetic transmitters(acetylcholine) slow down the heart rate. It works by affecting the nodal tissue. The symp and parasymp innervate the heart as a whole, which is important because they affect the strength of contractions, but the rate of beating is dependent on the SA node so we are only focusing on the innervation by the S/PS systems of the SA node. Starts with epi(bottom right corner), which is released from sympathetic nerves, and binds to a beta adrenergic receptor, which is going to have two effects. First is the one going up and to the left, phosphorylation of norepi allows it to bind to beta adrenergic receptor, activating a kinase A mechanism which phosphorylates the Ca channels, increasing their mean open time, which increases the Ca current (Ica), which lowers the threshold. Why would increasing the open time of Ca channel lower the threshold? Threshold is the voltage at which net inward current exceeds capacity of all outward carrying current channels to compensate. When you saturate the ability of the potassium channels to carry outward current, then you have a net depolarization. If you increase inward Ca current by prolonging the open time of the channels, that’s going to lower the threshold and lower the voltage at which you can get a regenerative response. Second effect is going horizontally left, through a cAMP mediated phosphorylation of the HCN channels (which are responsible for the inward current leak that produces the beginning of the pacemaker potential), increases its mean open time. That increases the inward funny current through the HCN channel, causing a faster depolarization. Both of the channels contribute to the pacemaker potential, the HCN channels in the more negative ranges, and the Ca channels in the more positive ranges. Red is normal, blue is with sympathetic stimulation – it crosses threshold sooner, and the slope of the pacemaker potential is steeper. So blue occurs earlier than it would have otherwise. As that repeats, the rate of the heartbeat goes up. Parasympathetic Stimulation Slows Heart Rate Starts with ACh release shown in bottom right corner. That attaches to a muscarinic ACh receptor, which is metabotropic. That, via a G- protein mechanism, activates a type of potassium channel called a GIRK channel(G-protein activated, inwardly rectifying K+ channel). The activation of GIRK channel causes an increase in the opening of this potassium channel. We are at hyperpolarized levels, so its open. The activation of the open channel reduces the slope of the pacemaker potential. Remember, the pacemaker potential is the balance between inward current carried by HCN channels in the negative ranges, and then Ca channels take over in the more positive ranges, but that’s counteracted by the outward potassium current. Here we are increasing the opening of K channels, letting more K out, so less inward current, and less of a slope. And a more slowly rising pacemaker potential, which reaches threshold(which ...

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