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 Gprotein 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 remains the same in this situation later so the heart rate is slowed down Electrical Conduction in the Heart On the right is a blown up picture of the right atrium The SA node is in purple and connected to them by gap junctions are the contractile cells SA nodal muscle tissue generates AP but doesn t contract To the right b c d e and f show the spread of electrical activity from the SA node out The AP spreads is the traditional method inward current through one cell causes the flow of outward current in another part of cell and that current flowing out across the membrane depolarizes it brings it to threshold and that AP travels In b the heart is in relaxation phase Purple dot is where the SA node is and it represents that an AP has just been generated c the AP has been generated and is spreading into the right atrium and the left atrium because across the interatrial septum the cells are all coupled by gap junctions The activity is spreading directly down across the surface of the right atrium and across and down through the left atrium so that by d we have both atria depolarized with an action potential In d the AP has arrived at another node the atroventricular node which it enters The AV node tissue also has an AP with a slow rate of rise just like the SA node So it spreads slowly through the AV node This is important because this delay of conduction allows time for the contraction of the atria to empty whatever blood it has into the ventricles From the AV node the AP goes into specialized elongated cardiac muscle cells that don t contract but do conduct action potentials quickly and those are the purkinje fibers and the bundles of fibers that form this conduction path are called the bundles of Hiis Coming off the AV node there is one bundle called the common bundle labeled AV bundle in the drawing and it separates into two main bundles in the interventricullar septum There s a left one and a right one These bundles of purkinje fibers conduct the AP down to the apex bottom of the heart And it spreads up around the sides and the purkinje fibers end and connect via gap junctions to the contractile fibers down in the apex of the heart This is fast About 4m sec in the purkinje fibers About 1m sec in the atria This arrangement of the Bundle of Hiis spreading the excitation from the atria down to the ventricles so that the contraction starts at the apex of the heart and spreads up is efficient because the openings from the ventricles through which blood is pumped out are at the top of the ventricles and having a wave of contractions moving up milks the blood out of the ventricles more efficiently So the action potential does not spread directly into the ventricles and this is because there is a layer of tissue between the atria and ventricles that are not coupled by gap junctions The ECG and Electrical Events in the Heart ECG electrocardiogram Figure to the right The red band is the AP and it starts at the apex and spreads up through the ventricles There are loops of current that go through the tissue but also extend out in the extracellular solution The loops of current ahead of the AP in the direction that it s going are flowing the in the opposite direction than the loops of current behind it So if you put a few electrodes on the body there will be some extracellular resistance between them and they will sample the current at the two points and the voltage