Electromechanical effects of anthopleurin-A (AP-A) on rabbit ventricular muscle: influence of driving frequency, calcium antagonists, tetrodotoxin, lidocaine and ryanodine.
1 Anthopleurin-A (AP-A 5 x 10(-9) M, 1 x 10(-8) M) caused a prolongation of action potential duration (APD) and an increase of contractile force in rabbit isolated ventricular muscle preparations.2 The prolongation of APD and the positive inotropic effect of AP-A (1 x 10(-8) M) were augmented by lowering the driving frequency from 2.0 to 0.2 Hz, resulting in an apparent negative staircase of contractile force in this frequency range. When the preparation was driven at an extremely low frequency (0.017 Hz), AP-A did not increase the contractile force, but caused a considerable prolongation of APD.3 Verapamil (1 x 10(-6) M) and nifedipine (1 x 10(-6) M) had no apparent influence on the APD prolongation by AP-A (5 x 10(-9) M, 1 x 10(-8) M). The positive inotropic effect of AP-A was also relatively well maintained even in the presence of these calcium antagonistic drugs when the preparation was driven at a lower frequency (0.2 Hz).4 Tetrodotoxin (TTX 2 x 10(-6) M) and lidocaine (1 x 10(-4) M) markedly inhibited both the APD prolongation and the positive inotropic effect of AP-A (1 x 10(-8) M).5 In the presence of ryanodine (2 x 10(-6) M), an agent which is known to interfere with calcium release from the intracellular activator pool, AP-A (1 x 10(-8) M) failed to cause its positive inotropic effect in spite of the marked prolongation of APD.6 These results suggest that the effects of AP-A on cardiac muscle are primarily mediated by the fast sodium inward current. Thus, delayed inactivation of sodium inward current may cause APD prolongation, and probably induces an alteration of intracellular calcium kinetics reflected by an increase of contractile force.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008012:Lidocaine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D012433:Ryanodine; D013779:Tetrodotoxin; C012746:anthopleurin-A; D008012:Lidocaine