Voltage-Dependent Modification of Vmax Recovery from Use-Dependent Block by Pirmenol in Guinea Pig Papillary Muscles

Abstract

Voltage-dependent modification of Vmax (the maximum upstroke velocity of the action potential) recovery from use-dependent block (UDB) by pirmenol was examined and compared with those observed with other Class I drugs using standard microelectrode techniques. A partial depolarization of the resting membrane by increasing extracellular potassium concentration ([K+]o) from 4 to 8 mM potentiated UDB at 2 Hz stimulation by any of the following drugs: pirmenol (10 microM), disopyramide (20 microM), pentisomide (50 microM), quinidine (20 microM), mexiletine (30 microM), and flecainide (5 microM). The recovery time constants from UDB of quinidine and mexiletine were prolonged and that of flecainide was unchanged in 8 mM [K+]o. However, the recovery time constant from UDB of pirmenol was shortened in high K+ solution, as observed with disopyramide and pentisomide. Thus, disopyramide and its analogues, including pirmenol, show a voltage dependency of recovery process, which is different from those of other class Ia, Ib, and Ic drugs. The main unblocking pathway of disopyramide and its analogues from sodium channels during diastolic interval may be different from that of other Class I drugs.