Slow inactivation of the sodium current in rabbit cardiac Purkinje fibres

Abstract

An analysis of the slowly inactivating Na current in rabbit cardiac Purkinje fibres was made, using the two-microelectrode voltage clamp technique. The existence of the slowly inactivating Na current was demonstrated by recording TTX-sensitive currents. The current was sensitive to Na withdrawal and could be blocked by 0.1 mM Cd. The current-voltage relation extended over a broad range of potentials, as negative as -85 mV. The time course of inactivation consisted of different phases, with time constants differing as much as three orders of magnitude. Time constants of the first phase of slow inactivation increased at more positive potentials. Non-inactivating Na currents were observed in the threshold region. Recovery from inactivation was less complex. The voltage dependency of inactivation could be described by a sigmoidal curve with a half maximum potential of -75.6 mV and a slope factor of 6.3 mV. Deactivation was fast. The results suggest that at the microscopic level the Na channel shows multiple states of inactivation. At the macroscopic level the slowly inactivating Na current plays an important role in determining diastolic potential, pacemaker activity and plateau duration, and is fundamental in explaining the effect of local anesthetics and frequency of stimulation on action potential duration.