Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine

作者：Schreiber Rainer; Faria Diana; Skryabin Boris V; Wanitchakool Podchanart; Rock Jason R; Kunzelmann Karl^*

来源：Pflugers Archiv-European Journal of Physiology, 2015, 467(6): 1203-1213.

DOI：10.1007/s00424-014-1559-2

• TMEM16A
• TMEM16F
• TMEM16K
• Anoctamin 1
• Anoctamin 6
• Anoctamin 10
• Ano1
• Ano6
• Ano10
• Ca2+-activated Cl- channels
• Colon
• Small intestine
• Ileum
• Jejunumchloride secretion

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.

• 出版日期2015-6