Effect of lidocaine on fast and slow inactivation of sodium current in rat ventricular cells

Abstract

The effects of lidocaine on the rapid inward sodium current (INA) of rat ventricular muscle were studied with the double sucrose gap voltage clamp technique. The action potential was abolished by a high concentration of lidocaine, but it was restored by membrane hyperpolarization. Under voltage clamp conditions, lidocaine blocked the INA. A hyperpolarizing conditioning pulse restored INA amplitude; a longer prepulse was more effective. At the steady state, inactivation of INA could be resolved into a fast (H) and a slow (j) component. Under lidocaine, the h infinity curve was shifted toward more negative potentials; the maximum shift (40.5 mV) was obtained t 425 microM lidocaine. The j infinity curve ran parallel to the h infinity curve and reached a plateau when h infinity became zero. This plateau value j infinity min, 0.9 +/- 0.09 (M +/- S.E.M.) in control conditions, was decreased by lidocaine in a dose-dependent way with a Km of 388 microM. The time constant of the recovery from slow inactivation was significantly reduced by lidocaine.