The cardiac action potential Two types of action potentials: 1.Fast response atrial and ventricular myocytes, Purkinje fibers Five phases: 0. Rapid upstroke 1.Early repolarization 2.Plateau 3.Final repolarization 4.Resting state 2.Slow response SA- and AV-node No phase 1 Less negative resting potential slower upstroke lower amplitude Relationship between action potential and contraction Peak of contraction at completion of repolarization. Duration of contraction parallels the duration of action potential. Resting membrane voltage Phase 4: g K is 100x more than g Na. Inward rectifier K channels i K1 current Inward rectifier K channels - i K1 current voltage-dependent open at more negative voltages. Inwardly rectified K current membrane recorded from cardiac myocyte when potential was changed from -80 mV to various test potentials. Inward current (flow of cations inside the cell negative). Outward current positive. Genesis of the AP upstroke (Phase O) Fast Na + channels (voltage- gated). Blocked by tetrodotoxin And some antiarhythmic drugs. Three states: Resting -closed Activated Inactivated (refractory period) Patch clamp recording of fast sodium current through two channels (Vm changed from -85 to -45 mV at the arrow and held throughout). The overall change in ionic conductance of entire cell membrane in a certain time reflects the number of channels that are open at that time. The single-channel conductance of one ion channel does not change with change in overall membrane conductance. Genesis of early repolarization (Phase 1) transient outward K + current i to Results from activation of transient outward K + current (i to ). Notch i to Notch variable in different parts of myocardium depends on density (expression) of i to channels. Genesis of the plateau (Phase 2) Activation of voltage dependent Ca 2+ channels: L-type long-lasting Predominant, activated at -20 mV, inactivate slowly. Blocked by verapamil, diltizem, amlodipine. Affected by catecholamines increased opening contractility. T-type Less abundant Inactivate more quickly Patch clamp rcording of Ca 2+ currents. Isoproterenol -adrenergic agonist. Genesis of the plateau (contd) Ca 2+ influx equal in size to K + efflux. g K lower than during phase 4! iK1 iK1 channels closed inward rectification! delayed rectifier K + channels i Kr - rapid i Ks - slow open delayed rectifier K + channels (i Kr - rapid and i Ks - slow). Genesis of final repolarization (Phase 3) Efflux of K + becomes larger than influx of Ca 2+ Initiation of repolarization: i to i to i Kr i Ks i Kr and i Ks iK1 At Vm less than -40 mV, iK1 channels open. iK1 Principal ionic currents regulating action potential in cardiac cell Restoration of ionic concentrations Na +, K + -ATPase 3Na + -1Ca 2+ -antiporter Plasma membrane Ca 2+ -ATPase In resting state Resting Vm is determined by: i K1 conductance for K + through i K1 channels c(K + ) outside c(K + ) outside can change under certain conditions myocardial ischemia Changes in the blood concentrations