ALTERED SUBTHRESHOLD SODIUM CURRENTS AND DISRUPTED FIRING PATTERNS INPURKINJE NEURONS OF SCN8A MUTANT MICE

Sodium currents and action potentials were characterized in Purkinje n eurons from ataxic mice lacking expression of the sodium channel Scn8a . Peak transient sodium current was similar to 60% of that in normal m ice, but subthreshold sodium current was affected much more. Steady-st ate current elicited by voltage ramps was reduced to similar to 30%, a nd resurgent sodium current, an unusual transient current elicited on repolarization following strong depolarizations, was reduced to 8%-18% . In jolting mice, with a missense mutation in Scn8a, steady-state and resurgent current were also reduced, with altered voltage dependence and kinetics. Both spontaneous firing and evoked bursts of spikes were diminished in cells from null and jolting mice. Evidently Scn8a chann els carry most subthreshold sodium current and are crucial for repetit ive firing.