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Coupling Gating with Ion Permeation in ClC Channels

In ClC chloride (Cl–) channels, unlike cation-selective ion channels, ion permeation is intimately coupled to fast gating. Recent research comparing the crystallographic structure of a bacterial ClC channel with functional studies of a Torpedo ClC channel suggests that gating depends on the negatively charged carboxyl group on a glutamate residue, which blocks the channel pore. In this model, the permeating Cl– competes with the carboxyl group for an anion-binding site in the channel pore. This model of Cl– competition with a glutamate gate helps explain the effect of intracellular Cl– on channel gating; the mechanism underlying the effects of extracellular Cl–, however, remains to be determined, as does the nature of the Cl– channel slow gate.