An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes

Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2563-8. doi: 10.1073/pnas.1012867108. Epub 2011 Jan 24.

Abstract

Regulatory volume decrease (RVD) is a key mechanism for volume control that serves to prevent detrimental swelling in response to hypo-osmotic stress. The molecular basis of RVD is not understood. Here we show that a complex containing aquaporin-4 (AQP4) and transient receptor potential vanilloid 4 (TRPV4) is essential for RVD in astrocytes. Astrocytes from AQP4-KO mice and astrocytes treated with TRPV4 siRNA fail to respond to hypotonic stress by increased intracellular Ca(2+) and RVD. Coimmunoprecipitation and immunohistochemistry analyses show that AQP4 and TRPV4 interact and colocalize. Functional analysis of an astrocyte-derived cell line expressing TRPV4 but not AQP4 shows that RVD and intracellular Ca(2+) response can be reconstituted by transfection with AQP4 but not with aquaporin-1. Our data indicate that astrocytes contain a TRPV4/AQP4 complex that constitutes a key element in the brain's volume homeostasis by acting as an osmosensor that couples osmotic stress to downstream signaling cascades.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 1 / genetics
  • Aquaporin 1 / metabolism
  • Aquaporin 4 / genetics
  • Aquaporin 4 / metabolism*
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • COS Cells
  • Calcium / metabolism
  • Cell Size*
  • Chlorocebus aethiops
  • Cricetinae
  • Humans
  • Mice
  • Mice, Knockout
  • Osmotic Pressure / physiology
  • Signal Transduction / physiology
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*

Substances

  • AQP1 protein, human
  • AQP4 protein, human
  • Aqp1 protein, mouse
  • Aqp4 protein, mouse
  • Aquaporin 4
  • TRPV Cation Channels
  • TRPV4 protein, human
  • Trpv4 protein, mouse
  • Aquaporin 1
  • Calcium