Properties of voltage-gated chloride channels of the ClC gene family

Abstract

We review the properties of ClC chloride channels, members of an expanding gene family originally discovered by the cloning of the ClC-0 chloride channel from Torpedo electric organ. There are at least nine different ClC genes in mammals, several of which seem to be expressed ubiquitously, while others are expressed in a highly specific manner (e.g. the muscle-specific ClC-1 channel and the kidney-specific ClC-K channels). The newly cloned rat ClC-4 is strongly expressed in liver and brain, but also in heart, muscle, kidney and spleen. ClC chloride channels are structurally unrelated to other channel proteins and have twelve putative transmembrane domains. They function as multimers with probably four subunits. Functional characterization is most advanced with ClC-0, ClC-1 (mutations which cause myotonia) and ClC-2, a swelling-activated chloride channel. Many of the new ClC family members cannot yet be expressed functionally.