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The ClC-0 Chloride Channel is a 'broken' Cl-/H+ Antiporter

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Date 2008 Jul 22
PMID 18641661
Citations 57
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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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References
1.
Estevez R, Schroeder B, Accardi A, Jentsch T, Pusch M . Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1. Neuron. 2003; 38(1):47-59. DOI: 10.1016/s0896-6273(03)00168-5. View

2.
Accardi A, Pusch M . Fast and slow gating relaxations in the muscle chloride channel CLC-1. J Gen Physiol. 2000; 116(3):433-44. PMC: 2233683. DOI: 10.1085/jgp.116.3.433. View

3.
Saviane C, Conti F, Pusch M . The muscle chloride channel ClC-1 has a double-barreled appearance that is differentially affected in dominant and recessive myotonia. J Gen Physiol. 1999; 113(3):457-68. PMC: 2222904. DOI: 10.1085/jgp.113.3.457. View

4.
Richard E, Miller C . Steady-state coupling of ion-channel conformations to a transmembrane ion gradient. Science. 1990; 247(4947):1208-10. DOI: 10.1126/science.2156338. View

5.
Chen M, Chen T . Side-chain charge effects and conductance determinants in the pore of ClC-0 chloride channels. J Gen Physiol. 2003; 122(2):133-45. PMC: 2229543. DOI: 10.1085/jgp.200308844. View