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This Article Full Text Full Text (PDF) All Versions of this Article: 572/1/173    most recent jphysiol.2005.102392v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yusef, Y. R. Articles by Sepúlveda, F. V. Search for Related Content PubMed PubMed Citation Articles by Yusef, Y. R. Articles by Sepúlveda, F. V. Related Collections Molecular and Genomic

¹ Centro de Estudios Científicos (CECS), Avda, Arturo Prat 514, Valdivia, Chile
² Universidad Austral de Chile, Valdivia, Chile

Functional and structural studies demonstrate that Cl^– channels of the ClC family have a dimeric double-barrelled structure, with each monomer contributing an identical pore. Studies with ClC-0, the prototype ClC channel, show the presence of independent mechanisms gating the individual pores or both pores simultaneously. A single-point mutation in the CBS-2 domain of ClC-0 has been shown to abolish slow gating. We have taken advantage of the high conservation of CBS domains in ClC channels to test for the presence of a slow gate in ClC-2 by reproducing this mutation (H811A). ClC-2-H811A showed faster opening kinetics and opened at more positive potentials than ClC-2. There was no difference in [Cl^–]_i dependence. Additional neutralization of a putative pore gate glutamate side chain (E207V) abolished all gating. Resolving slow and fast gating relaxations, however, revealed that the H811A mutation affected both fast and slow gating processes in ClC-2. This suggests that slow and fast gating in ClC-2 are coupled, perhaps with slow gating contributing to the operation of the pore E207 as a protopore gate.

(Received 24 November 2005; accepted after revision 2 February 2006; first published online 9 February 2006)
Corresponding author F. V. Sepúlveda: Centro de Estudios Cientificos (CECS), Av. Arturo Prat 514, Valdivia, Chile. Email: fsepulveda{at}cecs.cl

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