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DeepDyve Pubget Overpricing |
lüll Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding 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 BJ Clin Invest 2007[Nov]; 117 (11): 3453-62Here 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.|Adenosine Triphosphate/metabolism[MESH]|Animals[MESH]|Behavior, Animal/physiology[MESH]|Gene Deletion[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Mice, Knockout[MESH]|Motor Activity/physiology[MESH]|Rats[MESH]|TRPV Cation Channels/genetics/*metabolism[MESH]|Urinary Bladder/anatomy & histology/*metabolism[MESH]|Urination/*physiology[MESH]|Urodynamics[MESH]|Urothelium/cytology/metabolism[MESH] |