Resurgent current and voltage sensor trapping enhanced activation by a β-scorpion toxin solely in Na v1.6 channel: Significance in mice Purkinje neurons

Abstract

Resurgent currents are functionally crucial in sustaining the high frequency firing of cerebellar Purkinje neurons expressing Na v1.6 channels. β-Scorpion toxins, such as CssIV, induce a left shift in the voltage-dependent activation of Na v1.2 channels by "trapping" the IIS4 voltage sensor segment. We found that the dangerous Cn2 β-scorpion peptide induces both the left shift voltage-dependent activation and a transient resurgent current only in human Na v1.6 channels (among 1.1-1.7), whereas CssIV did not induce the resurgent current. Cn2 also produced both actions in mouse Purkinje cells. These findings suggest that only distinct β-toxins produce resurgent currents. We suggest that the novel and unique selectivity of Cn2 could make it a model drug to replace deep brain stimulation of the subthalamic nucleus in patients with Parkinson disease. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.