Modulation of voltage-gated K+ channels by the sodium channel β1 subunit

Hai M. Nguyen, Haruko Miyazaki, Naoto Hoshi, Brian J. Smith, Nobuyuki Nukina, Alan L. Goldin, K. George Chandy

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Voltage-gated sodium (NaV) and potassium(KV) channels are critical components of neuronal action potential generation and propagation. Here, we report that NaVβ1 encoded by SCN1b, an integral subunit of NaV channels, coassembles with and modulates the biophysical properties of KV1 and KV7 channels, but not KV3 channels, in an isoform-specific manner. Distinct domains of NaVβ1 are involved in modulation of the different KV channels. Studies with channel chimeras demonstrate that NaVβ1- mediated changes in activation kinetics and voltage dependence of activation require interaction of NaVβ1 with the channel's voltage-sensing domain, whereas changes in inactivation and deactivation require interaction with the channel's pore domain. A molecular model based on docking studies shows NaVβ1 lying in the crevice between the voltage-sensing and pore domains of KV channels, making significant contacts with the S1 and S5 segments. Cross-modulation of NaV and KV channels by NaVβ1 may promote diversity and flexibility in the overall control of cellular excitability and signaling.

Original languageEnglish
Pages (from-to)18577-18582
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number45
DOIs
Publication statusPublished - Nov 6 2012
Externally publishedYes

Keywords

  • Accessory subunit
  • Colocalization
  • Gating
  • Patch-clamp
  • Voltage-gated ion channels

ASJC Scopus subject areas

  • General

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