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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D010455:Peptides; D013779:Tetrodotoxin; C012746:anthopleurin-A; D012964:Sodium