From stones to bones: The biology of CIC chloride channels

Chloride (Cl^-) is the most abundant extracellular anion in multicellular organisms. Passive movement of Cl^-through membrane ion channels enables several cellular and physiological processes including transepithelial salt transport, electrical excitability, cell volume regulation and acidification of internal and external compartments. One family of proteins mediating Cl^- permeability, the CIC channels, has emerged as important for all of these biological processes. The importance of CIC channels has in part been realized through studies of inherited human diseases and genetically engineered mice that display a wide range of phenotypes from kidney stones to petrified bones. These recent findings have demonstrated many eclectic functions of CIC channels and have placed Cl^- channels in the physiological limelight.