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.
Cruz
J dos S
Jdos S
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Matsuda
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002018:Bufanolides / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D002018:Bufanolides; D015220:Calcium Channels; D015221:Potassium Channels; C055393:arenobufagin; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase