Permeation and Block of the Skeletal Muscle Chloride Channel, ClC-1, by Foreign Anions

• DOI: 10.1085/jgp.111.5.653
• Publication Date: 2002-07-26T16:50:20Z
• Authors: G.Y. Rychkov; M. Pusch; M.L. Roberts; T.J. Jentsch; A.H. Bretag
• Keywords: Chloride channel

A distinctive feature of the voltage-dependent chloride channels ClC-0 (the Torpedo electroplaque channel) and ClC-1 major skeletal muscle is that acts as a ligand to its own channel, regulating channel opening so controlling permeation species. We have now studied number foreign anions through using voltage-clamp techniques on Xenopus oocytes Sf9 cells expressing human (hClC-1) or rat (rClC-1) isoforms, respectively. From their effect gating, presented in this paper can be divided into three groups: impermeant poorly permeant not replace Cl− opener do block appreciably (glutamate, gluconate, HCO3−, BrO3−); open show significant (methanesulfonate, cyclamate); at regulatory binding site but impair passage pore (Br−, NO3−, ClO3−, I−, ClO4−, SCN−). The permeability sequence for rClC-1, SCN− ∼ ClO4− > Br− NO3− ClO3− I− >> BrO3− HCO3− methanesulfonate cyclamate glutamate, was different from determined blocking potency ability shift Popen curve, implying opens selectivity center situated closer external side. Channel by voltage dependent entirely accounted reduction single conductance. Minimum diameter estimated ∼4.5 Å. Anomalous mole-fraction effects found ratios conductance mixtures suggest multi-ion pore. Hydrophobic interactions with wall may explain discrepancies between measured permeabilities some size.