Evidence for two transient sodium currents in the frog node of Ranvier.

Abstract

Na current (INa) was monitored in isolated voltage-clamped frog nodes of Ranvier to analyze the pharmacological and kinetic properties of fast and slow phases of inactivation. Niflumic acid (0.1-10 mM) and tetrodotoxin [TTX] (0.3-30 nM) did not alter fast and slow inactivation time courses but preferentially reduced the amplitude of the fast phase of inactivation. The block of both phases of inactivation by niflumic acid and TTX was well described if one assumed that more than 1 molecule of drug reacted with 1 channel. Fast and slow currents, corresponding, respectively, to fast and slow phases of inactivation, reversed at different potentials, had different threshold voltages of activation and the slopes of their steady-state inactivation curves were different. The recovery from inactivation of the compound INa could be described by the sum of 2 exponentials (plus a delay) corresponding, respectively, to fast and slow currents. When calculated from INa recorded without and with niflumic acid or TTX, the slow current activated about three times more slowly than the fast current. Large prehyperpolarizations delayed both the activation and the inactivation of the fast current but only the activation of the slow current. Lowering the temperature decreased the fast current but increased the slow current. Evidently, the inactivatable Na current of the nodal membrane is made up to 2 components (INa,f and INa,s) corresponding to 2 different and interconvertible forms of the Na channel.