A decade of CLC chloride channels: Structure, mechanism, and many unsettled questions

ClC-type chloride channels are ubiquitous throughout the biological world. Expressed in nearly every cell type, these proteins have a host of biologic al functions. With nine distinct homologues known in eukaryotes, the ClCs r epresent the only molecularly defined family of chloride channels. CIC chan nels exhibit features of molecular architecture and gating mechanisms unpre cedented in other types of ion channels. They form two-pore homodimers, and their voltage-dependence arises not from charged residues in the protein, but rather via coupling of gating to the movement of chloride ions within t he pore. Because the functional characteristics of only a few ClC channels have been studied in detail, we are still learning which properties are gen eral to the whole family. New approaches, including structural analyses, wi ll be crucial to an understanding of ClC architecture and function.