Electrical Activity of the Heart Outline Ionic basis of resting potential Ionic basis of the fast response Ionic basis of the slow response Mechanism of rhythmicity Ionic basis of the resting potential Potential inside the cardiac cell is -90 mV relative to outside. Action potentials depolarize the cell and overshoot to +20 mV Fast response predominant in the atria and ventricle Slow response found in the SA and AV nodes Ionic basis of the resting potential The phases of the action potential are associated with changes in the permeability of the cell membrane to Na, K, and Ca. Permeability is controlled by ion channels. Ion [Extracellular] Na 145 [Intracellular] Potential (mV) 10 70 K 4 135 -94 Ca 2 10E-4 132 Ionic basis of the resting potential The resting cell membrane is relatively permeable to K via the inwardly rectifying K current. The diffusion gradient of K outward is balanced by impermeable anions that create an electrostatic force. The Nerst equation for K predicts a Ek of -94 which is slightly more negative than the resting potential due to slow Na leak If left, the leak would eventually depolarize the cell so the K/Na/ATPase acts to get rid of Na. Ionic basis of the fast response Genesis of the upstroke (Phase 0) Anything that raises the resting potential beyond threshold (-65 mV) will cause an action potential. Phase 0 due to Na inward. m gates open in Na channels as Vm becomes less negative. Na flows in due to the electric gradient until Vm = 0 then concentration gradient takes over. h gates close the channel due to the rising Vm h gates remain closed until partially repolarization (effective refractory period). Ionic basis of the fast response Genesis of early repolarization (Phase 1) Transient outward current of K causes a brief efflux of K because the interior is positive relative to exterior. Genesis of the plateau (Phase 2) Ca and some Na enters through slower activating and inactivating channels. Ca channels are voltage regulated and activated as Vm becomes less negative. Ionic basis of the fast response Genesis of the plateau (Phase 2) Two types of Ca channels; L and T type. L-type are long lasting and open when Vm -10 mV and enhanced by cAMP T-type are transient and open when Vm -70 mV but inactivate quickly. The positive Vm favours the efflux of K but K current drops which prevents excessive loss of K and loss of the plateau. Ionic basis of the fast response Genesis of final repolarization (Phase 3) Repolarization occurs when K efflux exceeds influx of Ca. Three K channels with different physiochemical properties are responsible for repolarization. Ionic basis of the fast response Restoration of ionic concentrations Ca is pumped out by a Na/Ca exchanger and Na is ejected by the Na/K/ATPase pump. Small component of Ca/ATPase. Ionic basis of the slow response Only difference is the loss of phase 0. During phase 4, the K channels gradually decrease their conductance (close) allowing unopposed Na leak inward that depolarizes the cell. When the Vm reaches a threshold, the Ca channels open to further depolarize. The K channels also open to restore polarity. Mechanism of Rhythmicity The SA node resting potential is only 55mV. The cell membrane is naturally leaky to Na and Ca. The fast Na channels are mostly inactive so only the Ca channel can open. The slow influx of Na causes the resting potential to gradually rise towards threshold. Questions??