Chloride channel

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1ots opm.png
Clc chloride channel
Identifiers
Symbol Voltage_CLC
Pfam PF00654
InterPro IPR014743
SCOP 1kpl
SUPERFAMILY 1kpl
TCDB 1.A.11
OPM superfamily 10
OPM protein 1ots
CDD cd00400

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

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. 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.

This family of ion 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. CLC-1 (P35523) 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 [3]. These proteins contain two CBS domains. Chloride channels are also important for maintaining safe ion concentrations within plant cells.[1]

Pathology[edit]

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. CLCNKB 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 CLCN5 are implicated.

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

Cystic fibrosis is caused by mutations in the CFTR gene, which prevents the proper folding of the protein and subsequent degradation, resulting in decreased numbers of chloride channels in the body. This causes the buildup of mucus in the body and chronic infections.

Functions[edit]

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 are not like 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.[2]

Commercial Applications[edit]

Some organic materials disrupt chloride channels in fleas, causing death. 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.

Human genes[edit]

See also[edit]

References[edit]

  1. ^ Li WY, Wong FL, Tsai SN, Phang TH, Shao G, Lam HM (June 2006). "Tonoplast-located GmCLC1 and GmNHX1 from soybean enhance NaCl tolerance in transgenic bright yellow (BY)-2 cells". Plant Cell Environ. 29 (6): 1122–37. doi:10.1111/j.1365-3040.2005.01487.x. PMID 17080938. 
  2. ^ Suzuki M, Morita T, Iwamoto T (January 2006). "Diversity of Cl Channels". Cell. Mol. Life Sci. 63 (1): 12–24. doi:10.1007/s00018-005-5336-4. PMC 2792346. PMID 16314923. 

Further reading[edit]

External links[edit]