Mechanism of accelerated current decay caused by an episodic ataxia type-1-associated mutant in a potassium channel pore.

ABSTRACT: In Kv1.1, single point mutants found below the channel activation gate at residue V408 are associated with human episodic ataxia type-1, and impair channel function by accelerating decay of outward current during periods of membrane depolarization and channel opening. This decay is usually attributed to C-type inactivation, but here we provide evidence that this is not the case. Using voltage-clamp fluorimetry in Xenopus oocytes, and single-channel patch clamp in mouse ltk- cells, of the homologous Shaker channel (with the equivalent mutation V478A), we have determined that the mutation may cause current decay through a local effect at the activation gate, by destabilizing channel opening. We demonstrate that the effect of the mutant is similar to that of trapped 4-aminopyridine in antagon

SUBMITTER: Peters CJ 

PROVIDER: S-EPMC6623802 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature