Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions. Several families of voltage-gated channels and ligand-gated channels (e.g., the CaCC families) have been characterized in humans. Voltage-gated chloride channels perform numerous crucial physiological and cellular functions, such as controlling pH, volume homeostasis, transporting organic solutes, regulating cell migration, proliferation, and differentiation. Based on sequence homology the chloride channels can be subdivided into a number of groups. General functions Voltage-gated chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels conduct or other anions such as . The structure of these channels are not like other known channels. The chloride channel subunits contain between 1 and 12 transmembrane segments. Some chloride channels are activated only by voltage (i.e., voltage-gated), while others are activated by , other extracellular ligands, or pH. CLC family The CLC family of chloride channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three CLC subfamilies are found in animals. CLCN1 is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney. These proteins contain two CBS domains. Chloride channels are also important for maintaining safe ion concentrations within plant cells. Structure and mechanism The CLC channel structure has not yet been resolved, however the structure of the CLC exchangers has been resolved by x-ray crystallography. Because the primary structure of the channels and exchangers are so similar, most assumptions about the structure of the channels are based on the structure established for the bacterial exchangers. Each channel or exchanger is composed of two similar subunits—a dimer—each subunit containing one pore. The proteins are formed from two copies of the same protein—a homodimer—though scientists have artificially combined subunits from different channels to form heterodimers. Each subunit binds ions independently of the other, meaning conduction or exchange occur independently in each subunit. Each subunit consists of two related halves oriented in opposite directions, forming an ‘antiparallel’ structure. These halves come together to form the anion pore.