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TMEM16A confers receptor-activated calcium-dependent chloride conductance
TMEM16A confers receptor-activated calcium-dependent chloride conductance
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TMEM16A confers receptor-activated calcium-dependent chloride conductance
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TMEM16A confers receptor-activated calcium-dependent chloride conductance
TMEM16A confers receptor-activated calcium-dependent chloride conductance

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TMEM16A confers receptor-activated calcium-dependent chloride conductance
TMEM16A confers receptor-activated calcium-dependent chloride conductance
Journal Article

TMEM16A confers receptor-activated calcium-dependent chloride conductance

2008
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Overview
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. TMEM16A (anoctamin 1) as a calcium-activated channel Calcium-activated chloride channels play a fundamental role in many physiological processes, but their molecular identity has so far evaded characterization. This paper shows that the transmembrane protein TMEM16A, also known as anoctamin 1 or ANO1, is a Ca 2+ -activated chloride channel. TMEM16A has a novel trimeric structure composed of eight transmembrane domains, very different from all previously characterized ionic channels. Its knock-down reduced native Ca 2+ activated chloride currents and impairs salivary secretion in mice.