title: Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding.
abstract: 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.
authors.affiliation: Department of Urology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gevaert
authors.forename: Joris
authors.initials: J
authors.lastname: Vriens
authors.forename: Andrei
authors.initials: A
authors.lastname: Segal
authors.forename: Wouter
authors.initials: W
authors.lastname: Everaerts
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Karel
authors.initials: K
authors.lastname: Talavera
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Owsianik
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Liedtke
authors.forename: Dirk
authors.initials: D
authors.lastname: Daelemans
authors.forename: Ilse
authors.initials: I
authors.lastname: Dewachter
authors.forename: Fred
authors.initials: F
authors.lastname: Van Leuven
authors.forename: Thomas
authors.initials: T
authors.lastname: Voets
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ridder
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000378:metabolism*; D014554:Urination / Q000502:physiology*; D014563:Urodynamics; D019459:Urothelium / Q000166:cytology / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D000255:Adenosine Triphosphate