EFFECTS OF CA2- PROLONGATION OF LATE-PHASE-4 DEPOLARIZATION BY EFONIDIPINE( CHANNEL ANTAGONISTS ON SINUS NODE )

Effects of various Ca2+ channel antagonists on the action potential co nfiguration of rabbit sino-atrial node tissue were examined with stand ard microelectrode techniques. All Ca2+ channel antagonists decreased the maximum rate of phase 0 depolarization ((V) over dot(max)) and inc reased the cycle length. The potency order to increase the cycle lengt h was nisoldipine = verapamil > nifedipine = clentiazem > efonidipine > diltiazem. The potency order to decrease (V) over dot(max) and to sh ift the threshold potential to a positive direction was the same as th at to increase the cycle length, indicating that the major mechanism o f negative chronotropism was inhibition of the L-type Ca2+ current. Al l Ca2+ channel antagonists except efonidipine shifted the maximum dias tolic potential to the positive direction, decreased the action potent ial amplitude and prolonged the action potential duration. The effects of nifedipine were slightly weaker than those of other drugs when com pared at equally bradycardiac concentrations. These differences may re flect differences in drug effects on currents other than the L-type Ca 2+ current. A characteristic feature of efonidipine was selective supp ression of the later phase of pacemaker depolarization with no effect on action potential amplitude and duration. Similar suppression of the later phase was observed with 50 mu M Ni2+, which is reported to inhi bit the T-type, but not L-type, Ca2+ current. Thus, efonidipine appear s to suppress selectively the later phase of pacemaker depolarization through inhibition of both L- and T-type Ca2+ currents, which may be t he underlying mechanism for its reported potent negative chronotropic but weak inotropic activity. (C) 1997 Elsevier Science B.V.