Effects of calcium channel blockers on ouabain-induced oscillatory afterpotentials in organ-cultured young embryonic chick hearts

Abstract

Ouabain induces oscillatory afterpotentials (OAPs) in organ-cultured young Since increased [Ca] i resulting from an inhibition of the Na pump by ouabain triggers oscillatory movements of Ca 2+ (i.e. OAPs) intracellularly, Ca 2+ influx through the cell membrane, which tends to increase [Ca] i, may be important in developing the OAPs. Therefore, in the present experiments, effects of calcium channel blockers on ouabain-induced OAPs in organ-cultured 3 day old embryonic chick hearts were examined. Automaticity was suppressed by elevating [K] ° to 6 mM. To induce the OAPs, the preparations were stimulated (0.5 Hz) in the presence of ouabain (2.5–6.3 μM). The calcium channel blockers (10 μM) depressed the OAPs in the following order of potency: bepridil > verapamil > nifedipine > diltiazem. This order of potency of the calcium channel blockers in depressing the OAPs was the same as that for drug penetration into the cells, but different from that for depressing slow action potentials: nifedipine > diltiazem > verapamil > bepridil (our previous findings). These results suggest that an intracellular site of action of the calcium channel blockers is important for depression of the OAPs, and suppression of the slow inward Ca 2+ current cannot be the sole mechanism for suppression of the OAPs by these drugs.