Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate

Manuel Covarrubias, Aguan Wei, Lawrence Salkoff, Tapan B. Vyas

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

The effect of protein kinase C (PKC) on rapid N-type inactivation of K+ channels has not been reported previously. We found that PKC specifically eliminates rapid inactivation of a cloned human A-type K+ channel (hKv3.4), converting this channel from a rapidly inactivating A type to a noninactivating delayed rectifier type. Biochemical analysis showed that the N-terminal domain of hKv3.4 is phosphorylated in vitro by PKC, and mutagenesis experiments revealed that two serines within the inactivation gate at the N-terminus are sites of direct PKC action. Moreover, mutating one of these serines to aspartic acid mimics the action of PKC. Serine phosphorylation may thus prevent rapid inactivation by shielding basic residues known to be critical to the function of the inactivation gate. The regulatory mechanism reported here may have substantial effects on signal coding in the nervous system.

Original languageEnglish
Pages (from-to)1403-1412
Number of pages10
JournalNeuron
Volume13
Issue number6
DOIs
StatePublished - Dec 1994

Fingerprint Dive into the research topics of 'Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate'. Together they form a unique fingerprint.

  • Cite this