Mechanism of ion permeation in skeletal muscle chloride channels

Christoph Fahlke*, Christine Dürr, Alfred L. George

*Corresponding author for this work

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Voltage-gated Cl- channels belonging to the ClC family exhibit unique properties of ion permeation and gating. We functionally probed the conduction pathway of a recombinant human skeletal muscle Cl- channel (hClC- 1) expressed both in Xenopus oocytes and in a mammalian cell line by investigating block by extracellular or intracellular I- and related anions. Extracellular and intracellular I- exert blocking actions on hClC-1 currents that are both concentration and voltage dependent. Similar actions were observed for a variety of other halide (Br-) and polyatomic (SCN-, NO3-, CH3SO3-) anions. In addition, I- block is accompanied by gating alterations that differ depending on which side of the membrane the blocker is applied. External I- causes a shift in the voltage-dependent probability that channels exist in three definable kinetic states (fast deactivating, slow deactivating, nondeactivating), while internal I- slows deactivation. These different effects on gating properties can be used to distinguish two functional ion binding sites within the hClC-1 pore. We determined K(D) values for I- block in three distinct kinetic states and found that binding of I- to hClC-1 is modulated by the gating state of the channel. Furthermore, estimates of electrical distance for I- binding suggest that conformational changes affecting the two ion binding sites occur during gating transitions. These results have implications for understanding mechanisms of ion selectivity in hClC-C, and for defining the intimate relationship between gating and permeation in ClC channels.

Original languageEnglish (US)
Pages (from-to)551-564
Number of pages14
JournalJournal of General Physiology
Volume110
Issue number5
DOIs
StatePublished - Nov 1997

Keywords

  • Chloride channel
  • Electrophysiology
  • Permeation
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology

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