Publication Date:
2008-08-30
Description:
Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Young Duk -- Cho, Hawon -- Koo, Jae Yeon -- Tak, Min Ho -- Cho, Yeongyo -- Shim, Won-Sik -- Park, Seung Pyo -- Lee, Jesun -- Lee, Byeongjun -- Kim, Byung-Moon -- Raouf, Ramin -- Shin, Young Ki -- Oh, Uhtaek -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Oct 30;455(7217):1210-5. doi: 10.1038/nature07313. Epub 2008 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18724360" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/*metabolism/pharmacology
;
Chloride Channels/chemistry/deficiency/genetics/*metabolism
;
Chlorides/*metabolism
;
Electric Conductivity
;
Gene Expression Profiling
;
Gene Expression Regulation
;
Humans
;
Intracellular Space/drug effects/metabolism
;
Ion Transport/drug effects
;
Mice
;
Oocytes/metabolism
;
Pilocarpine/pharmacology
;
RNA, Small Interfering/genetics/metabolism
;
Rats
;
Receptors, G-Protein-Coupled/*metabolism
;
Salivation/drug effects
;
Xenopus
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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