USE-DEPENDENT BLOCK AND RECOVERY OF NA⁺ CHANNELS BY CLASS IC ANTIARRHYTHMIC DRUGS (FLECAINIDE AND ETHACIZIN) IN CANINE VENTRICULAR MUSCLE

Abstract

Electrophysiological effects of flecainide and ethacizin (class Ic antiarrhythmic drugs) were examined using conventional microelectrode techniques. Flecainide significantly depressed the maximum rate of depolarization (⩒max) at 3x10⁻⁶M, and depolarized the resting potential (RP) at 10⁻⁵M, in a concentration-dependent manner. Ethacizin depressed ⩒max at 10⁻⁶M, and depolarized RP at 10⁻⁵M, significantly. However, both drugs did not affect the effective refractory period (ERP) nor the action potential duration (75% repolarization, APD₇₅). Both also had no effect on the action potential amplitude (APA). On the other hand, the drugs caused a use (or rate)-dependent block of ⩒max, and their time constants of onset of inhibition (at 3 Hz) were slow ; 6.3±1.2 msec (n=10) in the presence of flecainide (10⁻⁵M), and 6.0±1.6 msec (n=6) in the presence of ethacizin (10⁻⁵M). The time constants of the recovery were also so late : 12.2±2.5 sec (n=3) for flecainide (10⁻⁵M), and 27.1±13.3 sec (n=3) for ethacizin (2x10⁻⁶M), These results indicate that both antiarrhythmic drugs, flecainide and ethacizin, have no effect on APD₇₅ and ERP, but possess the characteristics for very slow kinetics of the use-dependent block and the recovery for fast Na⁺ channels of cardiac muscles. Ethacizin produces slower kinetics for the Na⁺ channels than flecainide.