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http://hdl.handle.net/1942/30286
Title: | Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. | Authors: | Gevaert, Thomas Vriens, Joris Segal, Andrei Everaerts, Wouter Roskams, Tania Talavera, Karel Owsianik, Grzegorz Liedtke, Wolfgang Daelemans, Dirk DEWACHTER, Ilse Van Leuven, Fred Voets, Thomas De Ridder, Dirk Nilius, Bernd |
Issue Date: | 2007 | Publisher: | AMER SOC CLINICAL INVESTIGATION INC | Source: | The Journal of clinical investigation, 117 (11) , p. 3453-62 -3462 | 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. | Keywords: | Heat-Evoked Activation;Urinary-Bladder;Mice Lacking;Vanilloid Receptor;P2x Receptors;Expression;Temperature;Rat;Urothelium;Sensation | Document URI: | http://hdl.handle.net/1942/30286 | DOI: | 10.1172/JCI31766 | ISI #: | 000250676000038 | Rights: | Open Access. 2020 American Society for Clinical Investigation | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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31766.2-20150304094807-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf | Published version | 1.1 MB | Adobe PDF | View/Open |
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