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ClC chloride channels viewed through a transporter lens

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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Figure 1: Structure of ClC-ec1.
Figure 2: A continuous single-channel recording of ClC-0.
Figure 3: A degraded-transporter model. Diagram of one subunit of a ClC channel showing a model of ClC channel fast gating.

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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.

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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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Miller, C. ClC chloride channels viewed through a transporter lens. Nature 440, 484–489 (2006). https://doi.org/10.1038/nature04713

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