Chloride channel 1513442 225415446 2008-07-13T15:50:30Z Boghog2 2428506 /* Human genes */ alphabetizing {{Pfam_box | Symbol = Voltage_CLC | Name = | image =1ots opm.gif | width =250 | caption =Clc chloride channel | Pfam= PF00654 | InterPro= IPR014743 | SMART= | Prosite = | SCOP = 1kpl | TCDB = 1.A.11 | OPM family= 10 | OPM protein= 1ots | PDB= {{PDB3|1kpl}}C:88-438 {{PDB3|2fed}}A:88-438 {{PDB3|2fec}}B:88-438 {{PDB3|1kpk}}F:88-438 {{PDB3|2fee}}A:88-438 {{PDB3|2exy}}B:88-438 {{PDB3|1otu}}B:88-438 {{PDB3|1ots}}A:88-438 {{PDB3|1ott}}B:88-438 {{PDB3|2ez0}}B:88-438 {{PDB3|2exw}}B:88-438 }} '''Chloride channels''' are a superfamily of poorly understood [[ion channel]]s 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 ({{UniProt|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 {{Pfam|PF00571}} domains. ==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<sup>-</sup> as well as other anions such as HCO<sub>3</sub><sup>-</sup>, I<sup>-</sup>, SCN<sup>-</sup>, and NO<sub>3</sub><sup>-</sup>. 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 Ca<sup>2+</sup>, extracellular ligands, and pH among other modulators.<ref name="pmid16314923">{{cite journal | author = Suzuki M, Morita T, Iwamoto T | title = Diversity of Cl<sup>-</sup> channels | journal = Cell. Mol. Life Sci. | volume = 63 | issue = 1 | pages = 12–24 | year = 2006 | month = January | pmid = 16314923 | doi = 10.1007/s00018-005-5336-4 | url = | issn = }}</ref> ==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. ==Human genes== * [[CLCA1]], [[CLCA2]], [[CLCA3]], [[CLCA4]] * [[CLCN1]], [[CLCN2]], [[CLCN3]], [[CLCN4]], [[CLCN5]], [[CLCN6]], [[CLCN7]], [[CLCNKA]], [[CLCNKB]] * [[CLIC1]], [[CLIC2]], [[CLIC3]], [[CLIC4]], [[CLIC5]], [[CLIC6]] * [[CLNS1A]], [[CLNS1B]] ==See also== * [[Cystic fibrosis transmembrane conductance regulator]] ==External links== * {{UMichOPM|families|superfamily|10}} - Clc Chloride channels * {{MeshName|Chloride+channels}} ==References== * <references/> ==Further reading== * {{cite journal | author = Schmidt-Rose T, Jentsch TJ | title = Reconstitution of functional voltage-gated chloride channels from complementary fragments of CLC-1 | journal = J. Biol. Chem. | volume = 272 | issue = 33 | pages = 20515–21 | year = 1997 | month = August | pmid = 9252364 | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9252364 | issn = }} * {{cite journal | author = Zhang J, George AL Jr, Griggs RC, Fouad GT, Roberts J, Kwieciński H, Connolly AM, Ptácek LJ | title = Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita | journal = Neurology | volume = 47 | issue = 4 | pages = 993–8 | year = 1996 | month = October | pmid = 8857733 | url = | issn = }} * {{cite journal | author = Mindell JA, Maduke M | title = ClC chloride channels | journal = Genome Biol. | volume = 2 | issue = 2 | pages = REVIEWS3003 | year = 2001 | pmid = 11182894 | pmc = 138906 | doi = | url = http://genomebiology.com/1465-6906/2/REVIEWS3003 | issn = }} {{Ion channels}} [[Category:Ion channels]] [[Category:Transmembrane proteins]] [[Category:Protein domains]] [[Category:Protein families]] [[de:Chloridkanal]]