title: Anion permeation in human ClC-4 channels.
abstract: ClC-4 and ClC-5 are mammalian ClC isoforms with unique ion conduction and gating properties. Macroscopic current recordings in heterologous expression systems revealed very small currents at negative potentials, whereas a substantially larger instantaneous current amplitude and a subsequent activation were observed upon depolarization. Neither the functional basis nor the physiological impact of these channel features are currently understood. Here, we used whole-cell recordings to study pore properties of human ClC-4 channels heterologously expressed in tsA201 or HEK293 cells. Variance analysis demonstrated that the prominent rectification of the instantaneous macroscopic current amplitude is due to a voltage-dependent unitary current conductance. The single channel amplitudes are very small, i.e., 0.10 +/- 0.02 pA at +140 mV for external Cl(-) and internal I(-). Conductivity and permeability sequences were determined for various external and internal anions, and both values increase for anions with lower dehydration energies. ClC-4 exhibits pore properties that are distinct from other ClC isoforms. These differences can be explained by assuming differences in the size of the pore narrowing and the electrostatic potentials within the ion conduction pathways.
authors.affiliation: RWTH Aachen, Institute of Physiology, Aachen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Hebeisen
authors.forename: Hannelore
authors.initials: H
authors.lastname: Heidtmann
authors.forename: Diego
authors.initials: D
authors.lastname: Cosmelli
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Barbara
authors.initials: B
authors.lastname: Poser
authors.forename: Ramon
authors.initials: R
authors.lastname: Latorre
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Alvarez
authors.forename: Christoph
authors.initials: C
authors.lastname: Fahlke
mesh_terms: D000838:Anions / Q000493:pharmacokinetics; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology*; D018118:Chloride Channels / Q000145:classification* / Q000502:physiology*; D002713:Chlorine / Q000502:physiology*; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007668:Kidney / Q000196:embryology* / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology*; D016062:Porosity; D011993:Recombinant Fusion Proteins / Q000145:classification / Q000502:physiology; D013045:Species Specificity
chemical_list: D000838:Anions; D018118:Chloride Channels; D011993:Recombinant Fusion Proteins; D002713:Chlorine