TMEM16A confers receptor-activated calcium-dependent chloride conductance

Young Duk Yang, Hawon Cho, Jae Yeon Koo, Min Ho Tak, Yeongyo Cho, Won Sik Shim, Seung Pyo Park, Jesun Lee, Byeongjun Lee, Byung Moon Kim, Ramin Raouf, Young Ki Shin, Uhtaek Oh

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Abstract

Calcium (Ca2+)-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 Ca2+-activated chloride channel that is activated by intracellular Ca2+ and Ca2+-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 Ca2+-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca2+-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca2+-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.

Original languageEnglish
Pages (from-to)1210-1215
Number of pages6
JournalNature
Volume455
Issue number7217
DOIs
Publication statusPublished - 2008 Oct 30

All Science Journal Classification (ASJC) codes

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    Yang, Y. D., Cho, H., Koo, J. Y., Tak, M. H., Cho, Y., Shim, W. S., Park, S. P., Lee, J., Lee, B., Kim, B. M., Raouf, R., Shin, Y. K., & Oh, U. (2008). TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature, 455(7217), 1210-1215. https://doi.org/10.1038/nature07313