Inactivation of the cardiac Na+ channels in guinea-pig ventricular cells through the open state.

1. The inactivation kinetics of the Na+ current were investigated using the improved oil-gap voltage clamp method in single ventricular cells of guinea-pig hearts. 2. Activation of the Na+ current was observed on depolarization more positive than -50 mV from a holding potential of -100 mV, and inactivation was complete during these depolarizations. The time course of current decay was fitted by a double exponential at potentials between -40 and -15 mV, and virtually by a single exponential at more positive potentials. The decay time courses examined either by the double-pulse protocol or the single-pulse protocol were similar. 3. The double-pulse protocol clearly revealed a sigmoidal onset of inactivation on depolarization. The initial delay of inactivation decreased with more positive potentials. The time course of double-pulse inactivation was reconstructed by integrating the Na+ current recorded by a continuous depolarization. 4. These findings are consistent with the hypothesis that the cardiac Na+ channel inactivates exclusively through the open state.