BISC 307L 1st Edition Lecture 24 Current Lecture Cardiovascular System Excitation Contraction Coupling and Relaxation o o A lot like skeletal muscle There are t tubules but not quite as extensive There is also the SR and channels and contractile proteins o 1 Red zone action potential in the sarcolemma of the fiber carried by sodium ions and calcium ions o 2 Calcium ions come through voltage gated calcium channels will bind to the ryanodine receptor and open it not mechanical like it is in skeletal muscle but it is due to calcium ions o 4 Calcium ions previously sequestered in SR are released Triggers contraction o 5 More calcium 90 released from SR and 10 released through plasma membrane through voltage gated channels o 6 Contraction o 8 Calcium pumps resequester calcium o 9 Ca Na antiport moves calcium out as well unlike skeletal muscle Sodium is pumped in o 10 The sodium being pumped in is maintained by the sodium potassium pump Catecholamine Modulation of Contraction o o How catecholamines modulate calcium function Epinephrine and norepi will increase cardiac output More forceful contraction and greater stroke volume mL contraction Catechoalmines bind to beta 1 adrenergic receptors in plasma membrane of cardiac muscle fibers and this activates a cAMP mediated phosphrylation kinase a of voltage gated ca2 channels on cytoplasmic side causes mean open time of channel to increase Increases calcium entry into the cell 1 Calcium that enters cell is sequestered into SR building up calcium stores in the SR and 2 The calcium coming in is the signal that triggers release of Ca2 from the SR more forceful contraction Second target of phosphorylation is phopholamban regulates the activity of Ca2 ATPase in SR phosphorylated phospholamban no longer inhibits the Ca2 ATPase pump builds up calcium stores and removes calcium from the cytosol and sequester into SR faster shortens transient elevated calcium levels in cell shorter contraction Shortening contraction time allows for more time spent in relaxation phase of cardiac cycle results in greater end diastolic volume when heart is filling with blood GREATER STROKE VOLUME Why more filling of the heart leads to greater stroke volume 1 More blood in heart more blood to pump out 2 The more its stretched the more it will forcefully pump Refresher on ionic Currents o o just a review slide remember this o potassium current always outward and sodium and calcium current are always going to be inward Action Potential in Cardiac Contractile Cells o o unusually long action potential due to the action of voltage gated ion channels the voltage gated Na channel conventional voltage gated Ca2 channel conventional and voltage gated K channel called the inwardly rectifying potassium channel meaning that it is open at negative potentials and closes when you depolarize unlike nerve potassium channels o THERE is NOT a delayed rectifier o 4 Just before action potential occurs Resting Inwardly rectifying K channels are open o 0 Rising phase due to influx of sodium rises fast depolarization is coming from adjacent cardiac muscle fiber spreading through the gap junctions o 1 At positive potentials Na channels start to be inactivated so get to be peak and stop going up K channels are closed o 2 Dip Na channels have closed and there are leakage channels that allow current to flow out so it repolarizes a little bit Inwardly rectifying K channels are not playing a role right now they are closed decrease in Pk Meanwhile voltage gated Ca2 channels have opened and they contribute a little bit of inward current this combination of a small outward current and a small inward Ca2 current makes the membrane hang out in this depolarized plateau important because during this Ca2 channels are open and contributing to contraction need to be open long for enough Ca2 release in the cell o 3 Repolarization starts to end plateau because many Ca2 channels have the property where Ca2 binding internally inactivates the Ca2 channels calcium inactivated Ca2 channels negative feedback when this happens there is no more inward calcium current so outward current starts to take over and gets more negative which opens the inwardly rectifying K channels Pacemaker or Slow Action Potential o o Heart is spontaneously active and begins its own action potentials occurs in pacemaker tissue 1 of the cells are the pacemaker tissues o This is action potential of pacemaker tissue why is the heart myogenic o In SA node Notice that resting potential is not as negative as other cells Spontaneous continuous depolarization that generates action potential which is slow and comes down and then starts repolarizing again Ionic Basis of Pacemaker and Action potential o o Ionic basis of what is going on in pace maker 1 Pacemaker potential is a depolarization that is slow so must be small number of current inward carried by Na ions through a channel that is known as the HCN channel hyperpolarization activated open at hyperpolarized levels and closes when depolarized cyclic nucleotide gated small cation channel small amount of outward K current but large amount of inward Na current net inward current This depolarizes the cell steadily to create the pacemaker potential 2 Closing of the HCN channel because depolarization closes it Voltage gated calcium channels of the L type are now depolarized enough to start opening so as the net inward current carried by Na diminishes the inward current of Ca2 ions increase 3 Many more voltage gated Ca2 channels are opened there are no Na channels Reaches threshold positive feedback happens and Ca2 channels continue to open Not that fast because not Na 4 There is a type of voltage gated K channel that opens with depolarization but unconventional because takes a long time to get to that opening point So they start opening creating outward current and repolarizes membrane 5 Around 30 or 40 the Ca2 channels close which makes it depolarize faster getting more and more negative 6 When negative enough the K channels now close and the HCN channels start opening again starting the depolarization again