Review Article | Published:

ClC chloride channels viewed through a transporter lens

Nature volume 440, pages 484489 (23 March 2006) | Download Citation

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Abstract

Since its discovery, the ClC family of chloride channels has presented biophysicists with unexpected behaviours and unusual surprises. The latest of these is the realization that not only does the family feature genuine chloride channels, it also includes proton-coupled chloride transporters, which move chloride ions and protons across the membrane in opposite directions. The crystal structure of such a transporter serves as a useful platform for understanding ClC channels, and features of chloride/proton exchange-transport may provide a key for comprehending voltage-dependent gating of the channels.

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Acknowledgements

I thank A. Accardi, T.-Y. Chen, R. Dutzler, Z. Lu and C. Thoreen for comments and criticisms on this manuscript.

Author information

Affiliations

  1. Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA. cmiller@brandeis.edu

    • Christopher Miller

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The author declares no competing financial interests.

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DOI

https://doi.org/10.1038/nature04713

Note added in proof The idea of voltage dependence of fast gating arising from intracellular proton movement was also recently suggested in studies of mutations at Gluex in CLC-0 (Raverso, S., Zifarelli, G., Aiello, R. & Pusch, M. J. Gen. Physiol 127, 51–65, 2006).  Author Information Reprints and permissions information is available at npg.nature.com/reprintsandpermissions.

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