Subunit stoichiometry of human muscle chloride channels

Christoph Fahlke, Timothy Knittle, Christina A. Gurnett, Kevin P. Campbell, Alfred L. George*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Voltage-gated Cl- channels belonging to the ClC family appear to function as homomultimers, but the number of subunits needed to form a functional channel is controversial. To determine subunit stoichiometry, we constructed dimeric human skeletal muscle Cl- channels in which one subunit was tagged by a mutation (D136G) that causes profound changes in voltage- dependent gating. Sucrose-density gradient centrifugation experiments indicate that both monomeric and dimeric hClC-1 channels in their native configurations exhibit similar sedimentation properties consistent with a multimeric complex having a molecular mass of dimer. Expression of the heterodimeric channel in a mammalian cell line results in a homogenous population of Cl- channels exhibiting novel gating properties that are best explained by the formation of heteromultimeric channels with an even number of subunits. Heteromultimeric channels were not evident in cells cotransfected with homodimeric WT-WT and D136G-D136G constructs excluding the possibility that functional hClC-1 channels are assembled from more than two subunits. These results demonstrate that the functional hClC-1 unit consists of two subunits.

Original languageEnglish (US)
Pages (from-to)93-104
Number of pages12
JournalJournal of General Physiology
Volume109
Issue number1
DOIs
StatePublished - Jan 1997

Keywords

  • chloride channel
  • electrophysiology
  • myotonia
  • skeletal muscle
  • subunit stoichiometry

ASJC Scopus subject areas

  • Physiology

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