Molecular dissection of gating in the ClC-2 chloride channel.

Published

Journal Article

The ClC-2 chloride channel is probably involved in the regulation of cell volume and of neuronal excitability. Site-directed mutagenesis was used to understand ClC-2 activation in response to cell swelling, hyperpolarization and acidic extracellular pH. Similar to equivalent mutations in ClC-0, neutralizing Lys566 at the end of the transmembrane domains results in outward rectification and a shift in voltage dependence, but leaves the basic gating mechanism, including swelling activation, intact. In contrast, mutations in the cytoplasmic loop between transmembrane domains D7 and D8 abolish all three modes of activation by constitutively opening the channel without changing its pore properties. These effects resemble those observed with deletions of an amino-terminal inactivation domain, and suggest that it may act as its receptor. Such a 'ball-and-chain' type mechanism may act as a final pathway in the activation of ClC-2 elicited by several stimuli.

Full Text

Duke Authors

Cited Authors

  • Jordt, SE; Jentsch, TJ

Published Date

  • April 1, 1997

Published In

Volume / Issue

  • 16 / 7

Start / End Page

  • 1582 - 1592

PubMed ID

  • 9130703

Pubmed Central ID

  • 9130703

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/16.7.1582

Language

  • eng

Conference Location

  • England