Characterization of three episodic ataxia mutations in the human Kv1.1 potassium channel

Episodic ataxia (EA) is a rare inherited neurological disorder due to mutation in the voltage-dependent Kv1.1 potassium channel. In nine unrelated families, a different missense point mutation at highly conserved positions has been reported. We have previously characterized six of the EA mutants. In this study, three recently identified mutations were introduced into the human Kv1.1 cDNA and expressed in Xenopus oocytes. Compared to wild type, T226A and T226M reduced the current amplitude by >95%, shifted the voltage dependence by 15 mV, and slowed activation and deactivation kinetics. Currents from G311S were ~25% of wild type, less steeply voltage-dependent and had more pronounced C-type inactivation. These altered gating properties will reduce the delayed-rectifier potassium current which may underlie the symptoms of EA.