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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gevaert, T; Vriens, J; Segal, A; Everaerts, W; Roskams, T; Talavera, K; Owsianik, G; Liedtke, W; Daelemans, D; Dewachter, I; Van Leuven, F; Voets, T; De Ridder, D; Nilius, B

Published Date

  • November 2007

Published In

Volume / Issue

  • 117 / 11

Start / End Page

  • 3453 - 3462

PubMed ID

  • 17948126

Pubmed Central ID

  • 17948126

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI31766

Language

  • eng