DEPRESSIVE EFFECTS OF ARENOBUFAGIN ON THE DELAYED RECTIFIER K+ CURRENT OF GUINEA-PIG CARDIAC MYOCYTES

The effects of a bufadienolide isolated from toad venom, arenobufagin, a potent Na+/K+ pump inhibitor, were studied in single guinea-pig ventricular cells in the whole-cell patch-clamp configuration. Arenobufagin (50 mu M) applied extracellularly decreased the amplitude of the delayed rectifier K+-current (I-dK) by 30% without affecting the gating kinetics. The L-type Ca2+ current was also depressed, but to a lesser extent. The inward rectifier K+ current was hardly affected. Ouabain and the internal dialysis of cells with the solution containing 20 mM Na+ depressed I-dK in a similar way as arenobufagin. On the other hand, arenobufagin also depressed I-dK when the Na+/K+ pump was already inhibited in the K+-free Tyrode solution. Therefore, both a direct effect on the channel and an indirect effect through the inhibition of the Na+/K+ pump may be involved in the depression of I-dK by arenobufagin.