Gating of the voltage-dependent chloride channel CIC-0 by the permeant anion.
Chloride channels of the ClC family are important for the control of membrane excitability, cell volume regulation, and possibly transepithelial transport. Although lacking the typical voltage-sensor found in cation channels, gating of ClC channels is clearly voltage-dependent. For the prototype Torpedo channel ClC-0 (refs 11-15) we now show that channel opening is strongly facilitated by external chloride. Other less permeable anions can substitute for chloride with less efficiency. ClC-0 conductance shows an anomalous mole fraction behaviour with Cl-/NO3- mixtures, suggesting a multi-ion pore. Gating shows a similar anomalous behaviour, tightly linking permeation to gating. Eliminating a positive charge at the cytoplasmic end of domain D12 changes kinetics, concentration dependence and halide selectivity of gating, and alters pore properties such as ion selectivity, single-channel conductance and rectification. Taken together, our results strongly suggest that in these channels voltage-dependent gating is conferred by the permeating ion itself, acting as the gating charge.
Centre for Molecular Neurobiology (ZMNH), Hamburg University, Germany.
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M
Pusch
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Ludewig
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Rehfeldt
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TJ
Jentsch
D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004594:Electrophysiology; D015640:Ion Channel Gating; D009154:Mutation; D009865:Oocytes; D011994:Recombinant Proteins; D014101:Torpedo; D014981:Xenopus
D018118:Chloride Channels; D002712:Chlorides; D011994:Recombinant Proteins