期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 467, 期 6, 页码 1203-1213出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-014-1559-2
关键词
TMEM16A; TMEM16F; TMEM16K; Anoctamin 1; Anoctamin 6; Anoctamin 10; Ano1; Ano6; Ano10; Ca2+-activated Cl- channels; Colon; Small intestine; Ileum; Jejunumchloride secretion
类别
资金
- DFG [SFB699A7]
- Wilhelm-Sander Stiftung [Ano6]
- Deutsche Krebshilfe [109438]
Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca2+ and opening of apical Cl- channels. In infants and young animals, but not in adults, Ca2+-activated chloride channels may cause secretory diarrhea during rotavirus infection. While detailed knowledge exists concerning the contribution of cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) channels, analysis of the role of Ca2+-dependent Cl- channels became possible through identification of the anoctamin (TMEM16) family of proteins. We demonstrate expression of several anoctamin paralogues in mouse small and large intestines. Using intestinal-specific mouse knockout models for anoctamin 1 (Ano1) and anoctamin 10 (Ano10) and a conventional knockout model for anoctamin 6 (Ano6), we demonstrate the role of anoctamins for Ca2+-dependent Cl- secretion induced by the muscarinic agonist carbachol (CCH). Ano1 is preferentially expressed in the ileum and large intestine, where it supports Ca2+-activated Cl- secretion. In contrast, Ano10 is essential for Ca2+-dependent Cl- secretion in jejunum, where expression of Ano1 was not detected. Although broadly expressed, Ano6 has no role in intestinal cholinergic Cl- secretion. Ano1 is located in a basolateral compartment/membrane rather than in the apical membrane, where it supports CCH-induced Ca2+ increase, while the essential and possibly only apical Cl- channel is CFTR. These results define a new role of Ano1 for intestinal Ca2+-dependent Cl- secretion and demonstrate for the first time a contribution of Ano10 to intestinal transport.
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