title: Two physically distinct pores in the dimeric ClC-0 chloride channel.
abstract: The Torpedo chloride channel ClC-0 is the prototype of a large family of chloride channels that have roles in transepithelial transport and in regulating electrical excitability and cell volume. ClC-0 opens in bursts with two identical conductance levels of approximately 8pS. 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 (approximately 1.5 pS). Coexpression with wild-type ClC-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 ClC-0 is a homodimer with two largely independent pores.
authors.affiliation: Centre for Molecular Neurobiology Hamburg, Hamburg University, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Ludewig
authors.forename: M
authors.initials: M
authors.lastname: Pusch
authors.forename: T J
authors.initials: TJ
authors.lastname: Jentsch
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000737:chemistry*; D004563:Electrochemistry; D015640:Ion Channel Gating; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D014101:Torpedo; D014981:Xenopus
chemical_list: D018118:Chloride Channels; D011994:Recombinant Proteins; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid