Gating of the voltage-dependent chloride channel CIC-0 by the permeant anion

Nature. 1995 Feb 9;373(6514):527-31. doi: 10.1038/373527a0.


Chloride channels of the ClC family are important for the control of membrane excitability, cell volume regulation, and possibly transepithelial transport. Although lacking the typical voltage-sensor found in cation channels, gating of ClC channels is clearly voltage-dependent. For the prototype Torpedo channel ClC-0 (refs 11-15) we now show that channel opening is strongly facilitated by external chloride. Other less permeable anions can substitute for chloride with less efficiency. ClC-0 conductance shows an anomalous mole fraction behaviour with Cl-/NO3- mixtures, suggesting a multi-ion pore. Gating shows a similar anomalous behaviour, tightly linking permeation to gating. Eliminating a positive charge at the cytoplasmic end of domain D12 changes kinetics, concentration dependence and halide selectivity of gating, and alters pore properties such as ion selectivity, single-channel conductance and rectification. Taken together, our results strongly suggest that in these channels voltage-dependent gating is conferred by the permeating ion itself, acting as the gating charge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorides / metabolism*
  • Electrophysiology
  • Ion Channel Gating*
  • Mutation
  • Oocytes
  • Recombinant Proteins
  • Torpedo
  • Xenopus


  • Chloride Channels
  • Chlorides
  • Recombinant Proteins