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

  • Rainer Schreiber
  • Diana Faria
  • Boris V. Skryabin
  • Podchanart Wanitchakool
  • Jason R. Rock
  • Karl KunzelmannEmail author
Ion channels, receptors and transporters


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.


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



This study was supported by DFG SFB699A7 and Wilhelm-Sander Stiftung Ano6 and Deutsche Krebshilfe Projekt 109438. We gratefully acknowledge the generous supply of the Ano6−/− mice by Prof. Dr. A. Vortkamp (Department Entwicklungsbiologie, University of Essen, Essen, Germany) and Ano-1 antibodies by Prof. Dr. Brian Harfe (University of Florida at Gainesville, Gainesville, USA).

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

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Supplementary Table S1 (DOCX 15 kb)
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Supplementary Fig. S1 (PDF 75 kb)
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Supplementary Fig. S2 (PDF 499 kb)
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Supplementary Fig. S3 (PDF 575 kb)
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Supplementary Fig. S4 (PDF 107 kb)
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Supplementary Fig. S5 (PDF 55 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Rainer Schreiber
    • 1
  • Diana Faria
    • 1
  • Boris V. Skryabin
    • 2
    • 6
  • Podchanart Wanitchakool
    • 1
  • Jason R. Rock
    • 3
    • 4
    • 5
  • Karl Kunzelmann
    • 1
    Email author
  1. 1.Institut für PhysiologieUniversität RegensburgRegensburgGermany
  2. 2.Institut für Experimentelle Pathologie (ZMBE)Westfälischen Wilhelms-Universität MünsterMünsterGermany
  3. 3.Department of AnatomyUniversity California, San FranciscoSan FranciscoUSA
  4. 4.Department of MedicineUniversity California, San FranciscoSan FranciscoUSA
  5. 5.Cardiovascular Research InstituteUniversity California, San FranciscoSan FranciscoUSA
  6. 6.Interdisciplinary Center for Clinical Research (IZKF)University of MünsterMünsterGermany

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