title: TMEM16A confers receptor-activated calcium-dependent chloride conductance.
abstract: 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.
authors: Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors: Young Duk
authors: YD
authors: Yang
authors: Hawon
authors: H
authors: Cho
authors: Jae Yeon
authors: JY
authors: Koo
authors: Min Ho
authors: MH
authors: Tak
authors: Yeongyo
authors: Y
authors: Cho
authors: Won-Sik
authors: WS
authors: Shim
authors: Seung Pyo
authors: SP
authors: Park
authors: Jesun
authors: J
authors: Lee
authors: Byeongjun
authors: B
authors: Lee
authors: Byung-Moon
authors: BM
authors: Kim
authors: Ramin
authors: R
authors: Raouf
authors: Young Ki
authors: YK
authors: Shin
authors: Uhtaek
authors: U
authors: Oh
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D018118:Chloride Channels / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004553:Electric Conductivity; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects; D014981:Xenopus
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D018118:Chloride Channels; D002712:Chlorides; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D010862:Pilocarpine; D002118:Calcium