Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding

J Clin Invest. 2007 Nov;117(11):3453-62. doi: 10.1172/JCI31766.


Here we provide evidence for a critical role of the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) in normal bladder function. Immunofluorescence demonstrated TRPV4 expression in mouse and rat urothelium and vascular endothelium, but not in other cell types of the bladder. Intracellular Ca2+ measurements on urothelial cells isolated from mice revealed a TRPV4-dependent response to the selective TRPV4 agonist 4alpha-phorbol 12,13-didecanoate and to hypotonic cell swelling. Behavioral studies demonstrated that TRPV4-/- mice manifest an incontinent phenotype but show normal exploratory activity and anxiety-related behavior. Cystometric experiments revealed that TRPV4-/- mice exhibit a lower frequency of voiding contractions as well as a higher frequency of nonvoiding contractions. Additionally, the amplitude of the spontaneous contractions in explanted bladder strips from TRPV4-/- mice was significantly reduced. Finally, a decreased intravesical stretch-evoked ATP release was found in isolated whole bladders from TRPV4-/- mice. These data demonstrate a previously unrecognized role for TRPV4 in voiding behavior, raising the possibility that TRPV4 plays a critical role in urothelium-mediated transduction of intravesical mechanical pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Behavior, Animal / physiology
  • Gene Deletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / physiology
  • Rats
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Urinary Bladder / anatomy & histology
  • Urinary Bladder / metabolism*
  • Urination / physiology*
  • Urodynamics
  • Urothelium / cytology
  • Urothelium / metabolism


  • TRPV Cation Channels
  • Trpv4 protein, mouse
  • Adenosine Triphosphate