EFFECTS OF CIBENZOLINE, A NEW CLASS IA ANTIARRHYTHMIC DRUG, ON VARIOUS MEMBRANE IONIC CURRENTS AND ACTION-POTENTIALS OF GUINEA-PIG VENTRICULAR CELLS

We examined the effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guin ea-pig single ventricular cells, using patch clamp techniques in whole -cell configuration. Action potentials and the membrane currents were evoked at a clamping rate of 0.2 Hz, and all experiments were performe d at 32-33 degrees C. 1) Cibenzoline (5, 10 and 30 mu M) decreased the Na+ current (I-Na), in a concentration-dependent manner. The concentr ation of the half-maximal inhibition (K-d) for I-Na was estimated to b e 7.8 mu M. 2) In addition to the inhibition of I-Na, this drug (5, 10 , and 30 mu M) decreased, in a concentration-dependent manner, all oth er membrane currents examined, such as L-type Ca2+ current (I-Ca), del ayed rectifier K+ current (I-K), and inward rectifier K+ current (I-K1 ). The K-d (apparent dissociation constant) values were 14.4 mu M for I-Ca, 23.0 mu M for I-K, and 33.7 mu M for I-K1 respectively. 3) Ciben zoline (5, 10, and 30 mu m) significantly shortended the action potent ial duration measured at both 30% and 90% repolarization without alter ing the resting membrane potential. From these findings, we conclude t hat apart from potent inhibitory effects on I-Na, cibenzoline possesse s multiple blocking effects on other currents, e.g., I-Ca, I-K and I-K 1, with a different potency (I-Na > I-Ca > I-K > I-K1) and with essent ially the same efficacy. These effects may explain, at least in part, the alleged, potent antiarrhythmic effects of this drug.