Effects of calcium channel blockers on ouabain-induced oscillatory afterpotentials in organ-cultured young embryonic chick hearts.
Ouabain induces oscillatory afterpotentials (OAPs) in organ-cultured young (3 day old) embryonic chick hearts. Since increased [Ca]i resulting from an inhibition of the Na pump by ouabain triggers oscillatory movements of Ca2+ (i.e. OAPs) intracellularly, Ca2+ 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]o to 6 mM. To induce the OAPs, the preparations were stimulated (0.5 Hz) in the presence of ouabain (2.5-6.3 microM). The calcium channel blockers (10 microM) depressed the OAPs in the following order of potency: bepridil greater than verapamil greater than nifedipine greater than 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 greater than diltiazem greater than verapamil greater than 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 Ca2+ current cannot be the sole mechanism for suppression of the OAPs by these drugs.
Kojima
M
M
Sperelakis
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D015764:Bepridil; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002642:Chick Embryo; D004110:Diltiazem / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010042:Ouabain / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011759:Pyrrolidines; D010042:Ouabain; D015764:Bepridil; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine