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PMID: 7993631 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Neuron ·Vol. 13 ·No. 6 ·1994-12-00 ·Pages 1403-12

Covarrubias M, Wei A, Salkoff L, Vyas TB

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.

Related Genes
hKv3.4
MeSH Terms
Amino Acid Sequence Animals Diglycerides/pharmacology In Vitro Techniques Ion Channel Gating Membrane Potentials Molecular Sequence Data Mutagenesis, Site-Directed Oocytes Phosphorylation Phosphoserine/metabolism Potassium Channels/metabolism Protein Kinase C/physiology Structure-Activity Relationship Tetradecanoylphorbol Acetate/pharmacology Xenopus laevis
Chemicals
Diglycerides Potassium Channels Phosphoserine Protein Kinase C Tetradecanoylphorbol Acetate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Covarrubias M
Department of Anatomy, Pathology, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
Wei A
Salkoff L
Vyas T B
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
DOI
10.1016/0896-6273(94)90425-1
Published
1994-12-00
Pages
1403-12
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2211371
Subset
IM
Grants
NINDS NIH HHS · R01 NS032337-08 · United States
NINDS NIH HHS · R01 NS032337-09A1 · United States
NINDS NIH HHS · NS24785 · United States
NINDS NIH HHS · R01 NS032337-11 · United States
NINDS NIH HHS · R01 NS032337-12 · United States
NINDS NIH HHS · R01 NS032337-10 · United States
NINDS NIH HHS · NS32337 · United States
NINDS NIH HHS · R01 NS032337 · United States
NINDS NIH HHS · R01 NS032337-06 · United States
NIAAA NIH HHS · AA07186 · United States
NIAAA NIH HHS · P50 AA007186 · United States
NINDS NIH HHS · R01 NS032337-07 · United States
NIAAA NIH HHS · T32 AA007463 · United States
External Links
PubMed source DOI: 10.1016/0896-6273(94)90425-1 PMC Full Text View journal details
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