Kinetic and stochastic properties of a persistent sodium current in mature guinea pig cerebellar Purkinje cells

Abstract

Whole cell voltage-clamp techniques were employed to characterize the sodium (Na) conductances in acutely dissociated, mature guinea-pig cerebellar Purkinje cells. Three phenomenological components were noted: two inactivating and a persistent component (I(Na)/(P)). All exhibited similar sensitivities to tetrodotoxin (TTX; IC50 ~3 nM). The inactivating Na current demonstrates two components with different rates of inactivation. The persistent component activates at a more negative membrane potential than the inactivating components and shows little inactivation during a 5-s pulse. The amplitude of the persistent Na conductance had a higher Q10 than the inactivating Na conductance (2.7 vs. 1.3). I(Na)/(P) rapidly activates (~1 ms) and deactivates (<0.2 ms) and like the fast component appears to be exclusively Na permeable. I(Na)/(P) is not a 'window' current because its range of activation exceeds the small overlap between the steady-state activation and inactivation characteristics of the inactivating current. Anomalous tail currents were observed during voltage pulses above -40 mV after a prepulse above -30 mV. The tails rose to a maximum inward current with a time constant of 1.5 ms and decayed to a persistent inward current with a time constant of 20 ms. The tails probably arose as a result of recovery from inactivation through the open state. The noise characteristics of I(Na)/(P) were anomalous in that the measured variance was lower at threshold voltages than would be predicted by a binomial model. The form of the variance could be partially accounted for by postulating that the maximum probability of activation of the persistent current was less than unity. The noise characteristics of I(Na)/(P) are such as to minimize noise near spike activation threshold and sharpen the threshold.