Chloride channel

Overview
Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members.

It is now recognised that chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. A number of different gene products have been shown to function as chloride channels. Based on sequence homology the chloride channels can be subdivided into a number of groups. The importance of one such group, the CLC family of chloride channels, can be seen from the diseases that develop when the channel does not function normally.

Pathology
Bartter's syndrome, which is associated with renal salt wasting and hypokalemic alkalosis, is due to the defective transport of chloride ions and associated ions in the thick ascending loop of Henle. CLC-Kb has been implicated.

Another inherited disease that affects the kidney organs is Dent's Disease, characterised by low molecular weight proteinuria and hypercalciuria where mutations in CLC-5 are implicated.

Thomsen disease is associated with domininate mutations and Becker disease with recessive mutations in CLCN1.

Functions
Chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels conduct Cl- as well as other anions such as HCO3-, I-, SCN-, and NO3-. The structure of these channels is also not other known channels. Chloride channel subunits contain between 1 and 12 transmembrane segments. Some members of this family are activated by voltage, while others are activated by Ca2+, extracellular ligands, and pH among other modulators.

Commercial Applications
Chloride channels are disrupted in fleas, causing death, with some organic materials. Selamectin is the active ingredient in Revolution, a topical insecticide and antihelminthic used on dogs and cats. Selamectin works by replacing glutamate which normally interacts with receptors that open chloride channels at muscle synapses found in parasites. Unlike glutamate, selamectin activates the chloride current without desensitization, thereby producing prolonged hyperpolarization and impaired muscle contraction.