Modulation of water efflux through functional interaction between TRPV4 and TMEM16A/anoctamin 1

FASEB J. 2014 May;28(5):2238-48. doi: 10.1096/fj.13-243436. Epub 2014 Feb 7.


Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable channel, is highly expressed in the apical membrane of choroid plexus epithelial cells (CPECs) in the brain. The function of TRPV4 is unknown. Here, we show physical and functional interaction between TRPV4 and anoctamin 1 (ANO1) in HEK293T cells and CPECs. Chloride currents induced by a TRPV4 activator (GSK1016790A) were markedly increased in an extracellular calcium-dependent manner in HEK293T cells expressing TRPV4 with ANO1, but not with ANO4, ANO6, or ANO10, the mRNAs of which were expressed in the choroid plexus. We also found physical interaction between TRPV4 and ANO1 in both HEK293T cells and choroid plexus. We observed that ANO1 was activated at a warm temperature (37°C) in HEK293T cells and that the heat-evoked chloride currents were markedly enhanced after GSK1016790A application in CPECs. Simultaneous stimulation by warmth and hyposmosis induced chloride current activation in wild-type, but not in TRPV4-deficient, CPECs. Cell volume changes were induced by ANO1-mediated chloride currents in parallel with membrane potential changes, and the cell volume was significantly decreased at negative membrane potentials by TRPV4-induced ANO1 activation. Thus, physical and functional interactions between TRPV4 and ANO1 can modulate water transport in the choroid plexus.

Keywords: calcium-activated chloride channel; cerebrospinal fluid; choroid plexus; hyposmosis; temperature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anoctamin-1
  • Calcium / metabolism
  • Chloride Channels / chemistry*
  • Chlorides / chemistry
  • Choroid Plexus / metabolism*
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Membrane Potentials
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Proteins / chemistry*
  • Patch-Clamp Techniques
  • Protein Binding
  • TRPV Cation Channels / chemistry*
  • Water / chemistry*


  • ANO1 protein, human
  • Anoctamin-1
  • Chloride Channels
  • Chlorides
  • Neoplasm Proteins
  • TRPV Cation Channels
  • TRPV4 protein, human
  • Water
  • Calcium