PROPERTIES OF VOLTAGE-GATED CHLORIDE CHANNELS OF THE CLC GENE FAMILY

We review the properties of ClC chloride channels, members of an expan ding gene family originally discovered by the cloning of the ClC-0 chl oride channel from Torpedo electric organ. There are at least nine dif ferent ClC genes in mammals, several of which seem to be expressed ubi quitously, while others are expressed in a highly specific manner (e.g . the muscle-specific ClC-1 channel and the kidney-specific ClC-K chan nels). The newly cloned rat ClC-4 is strongly expressed in liver and b rain, but also in heart, muscle, kidney and spleen. ClC chloride chann els are structurally unrelated to other channel proteins and have twel ve putative transmembrane domains. They function as multimers with pro bably 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.