title: Anion- and proton-dependent gating of ClC-4 anion/proton transporter under uncoupling conditions.
abstract: ClC-4 is a secondary active transporter that exchanges Cl(-) ions and H(+) with a 2:1 stoichiometry. In external SCN(-), ClC-4 becomes uncoupled and transports anions with high unitary transport rate. Upon voltage steps, the number of active transporters varies in a time-dependent manner, resembling voltage-dependent gating of ion channels. We here investigated modification of the voltage dependence of uncoupled ClC-4 by protons and anions to quantify association of substrates with the transporter. External acidification shifts voltage dependence of ClC-4 transport to more positive potentials and leads to reduced transport currents. Internal pH changes had less pronounced effects. Uncoupled ClC-4 transport is facilitated by elevated external [SCN(-)] but impaired by internal Cl(-) and I(-). Block by internal anions indicates the existence of an internal anion-binding site with high affinity that is not present in ClC channels. The voltage dependence of ClC-4 coupled transport is modulated by external protons and internal Cl(-) in a manner similar to what is observed under uncoupling conditions. Our data illustrate functional differences but also similarities between ClC channels and transporters.
authors.affiliation: Institut für Neurophysiologie, Medizinische Hochschule, Hannover, Germany.
authors.forename: Gökce
authors.initials: G
authors.lastname: Orhan
authors.forename: Christoph
authors.initials: C
authors.lastname: Fahlke
authors.forename: Alexi K
authors.initials: AK
authors.lastname: Alekov
mesh_terms: D000838:Anions / Q000378:metabolism / Q000494:pharmacology; D018118:Chloride Channels / Q000737:chemistry* / Q000378:metabolism*; D004560:Electricity; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D011522:Protons
chemical_list: D000838:Anions; C484312:CLCN4 protein, human; D018118:Chloride Channels; D011522:Protons