Chloride Channel

Chloride (Cl ) is the most abundant ion in nature. It is transported by several distinct families of chloride transporting proteins including chloride channels (ClC), ligand gated GABA and glycine receptors, cystic fibrosis conductance transmembrane regulators, cation chloride transporters, and chloride/bicarbonate exchangers. To date, there are nine known members of the human ClC family.  All ClC proteins have a transmembrane catalytic domain and most (all eukaryotic types and a few prokaryotic types) have a cytoplasmic regulatory domain. These are categorized into three groups based on their sequence homology. The first group comprises the Cl  channels: ClC-1, ClC-2, and the kidney-specific chloride channels ClC-Ka and ClC-Kb. The remaining proteins, classified as group 2 and 3, are electrogenic Cl /Hþ antiporters, whose distribution and physiological functions are distinct from the Cl  channel proteins. 
These five proteins (ClC-3, ClC-4, and ClC-5 in group 2; and ClC-6 and ClC-7 in group 3) are predominantly found in intravascular membranes of the endosomal-lysosomal pathway and are only expressed to a limited extent at the plasma membrane. The two best-characterized Cl /Hþ antiporters so far are ClC-5 and ClC-7. The group 3 antiporter proteins, ClC-6 and ClC-7, are thought to facilitate protein degradation by regulating Cl  ion concentration to ensure optimal function of the hydrolytic enzymes of late endosomes and lysosomal compartments. Evidence of a role for ClC proteins in human disease comes from genetic studies linking mutations in these proteins to the occurrence of many hereditary diseases. Clarification of these processes requires a thorough understanding of the behavior of ClC proteins at the molecular level.


1.Abeyrathne PD,et al. Biochimie. 2016 Sep-Oct;128-129:154-62.