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Two physically distinct pores in the dimeric CIC-0 chloride channel

Abstract

THE Torpedo chloride channel CIC-0 (ref. 1) is the prototype of a large family of chloride channels that have roles in transepithelial transport2 and in regulating electrical excitability3–6 and cell volume7. CIC-0 opens in bursts with two identical conductance levels of ˜8pS (refs 8–10). Hyperpolarization slowly increases the probability of bursts ('slow gating'), and depolarization increases channel opening within bursts ('fast gating'). Replacing serine 123 by threonine changes rectification, ion selectivity and gating, but retains the typical bursting behaviour with two identical independent albeit reduced, conductance states (˜1.5pS). Coexpression with wild-type CIC-0, either as covalently linked concatamers or as independent proteins, leads to bursting channels with two different pores. Our experiments strongly suggest that conductance, ion selectivity and 'fast' gating are determined only by the single subunit forming a single pore, independent from the attached pore; in contrast, 'slow' gating is a function of both subunits. Thus CIC-0 is a homodimer with two largely independent pores.

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Ludewig, U., Pusch, M. & Jentsch, T. Two physically distinct pores in the dimeric CIC-0 chloride channel. Nature 383, 340–343 (1996). https://doi.org/10.1038/383340a0

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