The ionic mechanism of prolongation of action potential duration of cardiac ventricular muscle by anthopleurin-A and its relationship to the inotropic effect.

Anthopleurin-A (AP-A) prolonged the duration of action potential and increased the developed tension of isolated guinea-pig and canine ventricular muscle. Voltage clamp experiments by using a single sucrose gap method were performed to investigate the ionic mechanism of the prolongation of the action potential in guinea-pig ventricular muscle. The prolongation of action potential by AP-A was accompanied by a decreased net outward current in a quasi-steady state. The slow inward current and the delayed potassium current were not changed by AP-A. The prolongation of action potential by AP-A was reversed by tetrodotoxin, thus it was concluded that AP-A induced tetrodotoxin-sensitive inward current which lasted long after the initial fast Na current. Modification of the AP-A-induced positive inotropic effect was also examined by using the canine blood-perfused ventricular muscle and was consistent with the above electrophysiological effects; tetrodotoxin, not nifedipine, suppressed percent changes produced by AP-A and also that by veratrine.