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The ClC-0 chloride channel is a 'broken' Cl−/H+ antiporter

Nature Structural & Molecular Biology volume 15, pages 805–810 (2008)Cite this article

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Abstract

Ion channels have historically been viewed as distinct from secondary active transporters. However, the recent discovery that the CLC 'chloride channel' family is made up of both channels and active transporters has led to the hypothesis that the ion-transport mechanisms of these two types of membrane proteins may be similar. Here we use single-channel analysis to demonstrate that ClC-0 channel gating (opening and closing) involves the transmembrane movement of protons. This result indicates that ClC-0 is a 'broken' Cl−/H+ antiporter in which one of the conformational states has become leaky for chloride ions. This finding clarifies the evolutionary relationship between the channels and transporters and conveys that similar mechanisms and analogous protein movements are used by both.

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Figure 1: ClC-0 gating.
Figure 2: Slow-gate closures recorded from patches with identical chloride gradients and different proton gradients.
Figure 3: The gating asymmetry ratio J+/J− as a function of free energy released from chloride transport, ΔGCl, and proton transport, ΔGH.
Figure 4: A possible model for non-equilibrium gating in ClC-0.

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  • 27 July 2008

    Supplementary information is available on the Nature Structural & Molecular Biology website

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Acknowledgements

We thank K. Matulef for help with the data analysis and R. Blaustein, B. Kobertz, R. Lewis, R. Reimer, J. Huguenard and members of the Maduke laboratory for comments on the manuscript. This work was supported by the US National Institutes of Health grant R01 GM070773 and by the Mathers Foundation. J.L. is supported by the Human Frontiers Science Program.

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  1. Department of Molecular and Cellular Physiology, Stanford University, 279 Campus Drive, Stanford, 94305, California, USA

    Jiří Lísal & Merritt Maduke

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  1. Jiří Lísal
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  2. Merritt Maduke
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J.L. collected the experimental data; J.L. and M.M. designed the experiments, analyzed the data and wrote the manuscript.

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Correspondence to Merritt Maduke.

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Lísal, J., Maduke, M. The ClC-0 chloride channel is a 'broken' Cl−/H+ antiporter. Nat Struct Mol Biol 15, 805–810 (2008). https://doi.org/10.1038/nsmb.1466

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