From stones to bones: The biology of CIC chloride channels

Chloride (Cl-) is the most abundant extracellular anion in multicellular or ganisms. Passive movement of Cl- through membrane ion channels enables seve ral cellular and physiological processes including transepithelial salt tra nsport, electrical excitability, cell volume regulation and acidification o f internal and external compartments. One family of proteins mediating Cl- permeability, the CIC channels, has emerged as important for all of these b iological processes. The importance of CIC channels has in part been realiz ed through studies of inherited human diseases and genetically engineered m ice 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.