CHARACTERIZATION OF 3 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 unr elated families, a different missense point mutation at highly conserv ed positions has been reported. We have previously characterized six o f the EA mutants. In this study, three recently identified mutations w ere introduced into the human Kv1.1 cDNA and expressed in Xertopus ooc ytes, Compared to mild type, T226A and T226M reduced the current ampli tude by >95%, shifted the voltage dependence by 15 mV, and slowed acti vation and deactivation kinetics. Currents from G311S were similar to 25% of wild type, less steeply voltage-dependent and had more pronounc ed C-type inactivation. These altered gating properties mill reduce th e delayed-rectifier potassium current which may underlie the symptoms of EA. (C) 1998 Federation of European Biochemical Societies.