title: Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine.
abstract: Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca(2+) and opening of apical Cl(-) channels. In infants and young animals, but not in adults, Ca(2+)-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 Ca(2+)-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 Ca(2+)-dependent Cl(-) secretion induced by the muscarinic agonist carbachol (CCH). Ano1 is preferentially expressed in the ileum and large intestine, where it supports Ca(2+)-activated Cl(-) secretion. In contrast, Ano10 is essential for Ca(2+)-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 Ca(2+) increase, while the essential and possibly only apical Cl(-) channel is CFTR. These results define a new role of Ano1 for intestinal Ca(2+)-dependent Cl(-) secretion and demonstrate for the first time a contribution of Ano10 to intestinal transport.
authors: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors: Rainer
authors: R
authors: Schreiber
authors: Diana
authors: D
authors: Faria
authors: Boris V
authors: BV
authors: Skryabin
authors: Podchanart
authors: P
authors: Wanitchakool
authors: Jason R
authors: JR
authors: Rock
authors: Karl
authors: K
authors: Kunzelmann
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D000075368:Anoctamins; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C531181:ANO1 protein, mouse; C576687:ANO6 protein, mouse; D000075369:Anoctamin-1; D000075368:Anoctamins; D018118:Chloride Channels; D002712:Chlorides; D049294:Phospholipid Transfer Proteins; D002118:Calcium