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Episodic ataxia (EA) is an autosomal dominant human disorder that produces persistent myokymia and attacks of generalized ataxia. Recently, familial EA has been linked to the voltage-dependen! delayed rectifier, Kvl. l, on chromosome 12. Six EA families have been identified that carry distinct Kvl. 1 missense mutations; all individuals are heteroxygous. Expression in Xenopus oocytes demonstrates that two of the EA subunits form homomerlc channels with altered gating properties. V408A channels have voltage dependence similar to that of wild-type channels, but with faster kinetics and increased C-type inactivation, while the voltage dependence of F184C channels is shifted 20 mV positive. The other four EA subunits do not produce functional homomeric channels but reduce the potassium current when coassembled with wild-type subunits. The results suggest a cellular mechanism underlying EA in which the …