Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding.
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.
Gevaert
Thomas
T
Department of Urology, University Hospital Gasthuisberg, Leuven, Belgium.
Vriens
Joris
J
Segal
Andrei
A
Everaerts
Wouter
W
Roskams
Tania
T
Talavera
Karel
K
Owsianik
Grzegorz
G
Liedtke
Wolfgang
W
Daelemans
Dirk
D
Dewachter
Ilse
I
Van Leuven
Fred
F
Voets
Thomas
T
De Ridder
Dirk
D
Nilius
Bernd
B
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
D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D000255:Adenosine Triphosphate