Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding.
Journal Article (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
- PMC2030459
International Standard Serial Number (ISSN)
- 0021-9738
Digital Object Identifier (DOI)
- 10.1172/JCI31766
Language
- eng
Conference Location
- United States