Expression and function of epithelial anoctamins

J Biol Chem. 2010 Mar 5;285(10):7838-45. doi: 10.1074/jbc.M109.065367. Epub 2010 Jan 7.


The calcium-activated chloride channel anoctamin1 (ANO1; TMEM16A) is fundamental for the function of epithelial organs. Mice lacking ANO1 expression exhibit transport defects and a pathology similar to cystic fibrosis. They also show a general defect of epithelial electrolyte transport. Here we analyzed expression of all ten members (ANO1-ANO10) in a broad range of murine tissues and detected predominant expression of ANO1, 6, 7, 8, 9, 10 in epithelial tissues, while ANO2, 3, 4, 5 are common in neuronal and muscle tissues. When expressed in Fisher Rat Thyroid (FTR) cells, all ANO proteins localized to the plasma membrane but only ANO1, 2, 6, and 7 produced Ca(2+)-activated Cl(-) conductance, as analyzed by ATP-induced iodide quenching of YFP fluorescence. In contrast ANO9 and ANO10 suppressed baseline Cl(-) conductance and coexpression of ANO9 with ANO1 inhibited ANO1 activity. Patch clamping of ANO-expressing FRT cells indicated that apart from ANO1 also ANO6 and 10 produced chloride currents, albeit with very different Ca(2+) sensitivity and activation time. We conclude that each tissue expresses a set of anoctamins that form cell- and tissue-specific Ca(2+)-dependent Cl(-) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Calcium / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Chloride Channels / metabolism*
  • Chlorides / metabolism*
  • Epithelium / metabolism*
  • Humans
  • Ion Channel Gating / physiology
  • Ionomycin / metabolism
  • Ionophores / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Patch-Clamp Techniques
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Rats
  • Tissue Distribution


  • Chloride Channels
  • Chlorides
  • Ionophores
  • Protein Isoforms
  • Ionomycin
  • Calcium