MODES OF THE NA CHANNEL BLOCKING ACTION OF PILSICAINIDE, A NEW ANTIARRHYTHMIC AGENT, IN CARDIAC-CELLS

Using a whole cell clamp technique, the blockade of sodium currents (I(Na)) by pilsicainide, a new antiarrhythmic agent, applied either intracellularly or extracellularly, was studied in single myocytes isolated from guinea pig right ventricle. Pilsicainide applied extracellularly inhibited the peak amplitude of I(Na) in concentration- (from 10(-5) M to 10(-4) M) and rate- (from 0.5 Hz to 3.0 Hz) dependent manners. The onset rate of the blockade in I(Na) was almost constant, independent of frequency of stimulus, but higher at high concentration of pilsicainide. The time constant in the recovery phase from I(Na) inactivation remained almost constant (65 to 75 msec) in the range of concentrations used. Similar results were obtained by intracellular application of 10(-3) M pilsicainide. Pilsicainide applied intracellularly inhibited I(Na) in a rate-dependent manner. The blocking potency of internally applied pilsicainide almost corresponded to that of external 10(-5) M pilsicainide. The onset rate of I(Na) inactivation (from 0.098/pulse to 0.130/pulse) and the recovery time constant (77 msec) was similar to those of external 10(-5) M pilsicainide. These results suggest that pilsicainide, irrespective of intra- or extracellular application, shares a common binding site to block I(Na) in cardiac myocytes.