Coupling gating with ion permeation in ClC channels

Abstract

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.