2. 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

3. Relationship between action potential and contraction Peak of contraction – at completion of repolarization. Duration of contraction parallels the duration of action potential.

5. 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.

6. 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.

7. 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.

8. 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 – β-adrenergic agonist.

9. Genesis of the plateau (cont’d) 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).

10. 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

11. Principal ionic currents regulating action potential in cardiac cell

12. Restoration of ionic concentrations Na +, K + -ATPase 3Na + -1Ca 2+ -antiporter Plasma membrane Ca 2+ -ATPase

13. 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