TMEM16A confers receptor-activated calcium-dependent chloride conductance.
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.
Yang
Young Duk
YD
Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Cho
Hawon
H
Koo
Jae Yeon
JY
Tak
Min Ho
MH
Cho
Yeongyo
Y
Shim
Won-Sik
WS
Park
Seung Pyo
SP
Lee
Jesun
J
Lee
Byeongjun
B
Kim
Byung-Moon
BM
Raouf
Ramin
R
Shin
Young Ki
YK
Oh
Uhtaek
U
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
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