Distinct functional stoichiometry of potassium channel β subunits

Jia Xu, Weifeng Yu, Jerry M. Wright, Ronald W. Raab, Min Li

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Shaker-type potassium channels play important roles in determining the electrical excitability of cells. The native channel complex is thought to be formed by four pore-forming α subunits that provide four interaction sites for auxiliary modulatory Kvβ subunits. Because Kvβ subunits possess diverse modulatory activities including either up-regulation or down-regulation of potassium currents, differential assembly of the α-β complex could give rise to diverse current properties. However, the detailed physical and functional stoichiometry of the α-β complex remains unknown. Kvβ1 subunits reduce potassium currents through inactivation, whereas Kvβ2 subunits enhance potassium currents by inhibiting the Kvβ1-mediated inactivation and at the same time by promoting the surface expression of certain potassium channels. In this report we show that Kvβ1 and Kvβ2 of the Shaker-type potassium channels display distinct functional stoichiometry to interact with the Kv1 α subunits, a subfamily of Shaker-type potassium channels. The interaction of Kvβ1 subunits with α subunits is consistent with the α4β(n) model, where n equals 0, 1, 2, 3, or 4, depending upon the relative concentration of α and β subunits. The α4β(n) stoichiometry allows for gradual changes of the Kvβ1-mediated inactivation. In contrast, Kvβ2 subunits self-associate to form oligomers and interact with the α subunits via α4β4 stoichiometry, which permits effective multivalent associations with α subunits. Such distinct functional stoichiometry of Kvβ1 and Kvβ2 provides a molecular mechanism that is well suited to their contrasting activities of up-regulation or down-regulation of potassium currents.

Original languageEnglish (US)
Pages (from-to)1846-1851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998
Externally publishedYes

ASJC Scopus subject areas

  • General

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