Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: Evidence for two mechanisms

We examined the kinetics of voltage-dependent sodium currents in cerebellar Purkinje neurons using whole-cell recording from dissociated neurons, Unli ke sodium currents in other cells, recovery from inactivation in Purkinje n eurons is accompanied by a sizeable ionic current. Additionally, the extent and speed of recovery depend markedly on the voltage and duration of the p repulse that produces inactivation. Recovery is faster after brief, large d epolarizations (e.g,, 5 ms at +30 mV) than after long, smaller depolarizati ons (e.g., 100 ms at -30 mV), On repolarization to -40 mV following brief, large depolarizations, a resurgent sodium current rises and decays in paral lel with partial, nonmonotonic recovery from inactivation. These phenomena can be explained by a model that incorporates two mechanisms of inactivatio n: a conventional mechanism, from which channels recover without conducting current, and a second mechanism, favored by brief, large depolarizations, from which channels recover by passing transiently through the open state, The second mechanism is consistent with voltage-dependent block of channels by a particle that can enter and exit only when channels are open. The sod ium current flowing during recovery from this blocked state may depolarize cells immediately after an action potential, promoting the high-frequency f iring typical of Purkinje neurons.