Molecular dissection of gating in the ClC-2 chloride channel

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Item Type:	Article
Title:	Molecular dissection of gating in the ClC-2 chloride channel
Creators Name:	Jordt, S.E. and Jentsch, T.J.
Abstract:	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.
Keywords:	Activation by pH, Ball-and-Chain, Cell Volume Regulation, Rectification, Swelling Activation, Animals, Rats
Source:	EMBO Journal
ISSN:	0261-4189
Publisher:	Oxford University Press
Volume:	16
Number:	7
Page Range:	1582-1592
Date:	1 April 1997
Official Publication:	https://doi.org/10.1093/emboj/16.7.1582
PubMed:	View item in PubMed

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