Subunit composition determines Kv1 potassium channel surface expression

Louis N. Manganas, James Trimmer

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

Shaker-related or Kv1 voltage-gated K+ channels play critical roles in regulating the excitability of mammalian neurons. Native Kv1 channel complexes are octamers of four integral membrane α subunits and four cytoplasmic β subunits, such that a tremendous diversity of channel complexes can be assembled from the array of α and β subunits expressed in the brain. However, biochemical and immunohistochemical studies have demonstrated that only certain complexes predominate in the mammalian brain, suggesting that regulatory mechanisms exist that ensure plasma membrane targeting of only physiologically appropriate channel complexes. Here we show that Kv1 channels assembled as homo- or heterotetrameric complexes had distinct surface expression characteristics in both transfected mammalian cells and hippocampal neurons. Homotetrameric Kv1.1 channels were localized to endoplasmic reticulum, Kv1.4 channels to the cell surface, and Kv1.2 channels to both endoplasmic reticulum and the cell surface. Heteromeric assembly with Kv1.4 resulted in dose-dependent increases in cell surface expression of coassembled Kv1.1 and Kv1.2, while coassembly with Kv1.1 had a dominant-negative effect on Kv1.2 and Kv1.4 surface expression. Coassembly with Kvβ subunits promoted cell surface expression of each Kv1 heteromeric complex. These data suggest that subunit composition and stoichiometry determine surface expression characteristics of Kv1 channels in excitable cells.

Original languageEnglish (US)
Pages (from-to)29685-29693
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number38
DOIs
StatePublished - Sep 22 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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