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 microM) applied extracellularly decreased the amplitude of the delayed rectifier K+ current (IdK) 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 IdK in a similar way as arenobufagin. On the other hand, arenobufagin also depressed IdK 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 IdK by arenobufagin.