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Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding.
J Clin Invest. 2007 Nov; 117(11):3453-62.JCI

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+Show Affiliations

Department of Urology, University Hospital Gasthuisberg, Leuven, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17948126

Citation

Gevaert, Thomas, et al. "Deletion of the Transient Receptor Potential Cation Channel TRPV4 Impairs Murine Bladder Voiding." The Journal of Clinical Investigation, vol. 117, no. 11, 2007, pp. 3453-62.
Gevaert T, Vriens J, Segal A, et al. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest. 2007;117(11):3453-62.
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. (2007). Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. The Journal of Clinical Investigation, 117(11), 3453-62.
Gevaert T, et al. Deletion of the Transient Receptor Potential Cation Channel TRPV4 Impairs Murine Bladder Voiding. J Clin Invest. 2007;117(11):3453-62. PubMed PMID: 17948126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. AU - Gevaert,Thomas, AU - Vriens,Joris, AU - Segal,Andrei, AU - Everaerts,Wouter, AU - Roskams,Tania, AU - Talavera,Karel, AU - Owsianik,Grzegorz, AU - Liedtke,Wolfgang, AU - Daelemans,Dirk, AU - Dewachter,Ilse, AU - Van Leuven,Fred, AU - Voets,Thomas, AU - De Ridder,Dirk, AU - Nilius,Bernd, PY - 2007/02/09/received PY - 2007/08/13/accepted PY - 2007/10/20/pubmed PY - 2008/4/3/medline PY - 2007/10/20/entrez SP - 3453 EP - 62 JF - The Journal of clinical investigation JO - J Clin Invest VL - 117 IS - 11 N2 - 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. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/17948126/Deletion_of_the_transient_receptor_potential_cation_channel_TRPV4_impairs_murine_bladder_voiding_ L2 - https://doi.org/10.1172/JCI31766 DB - PRIME DP - Unbound Medicine ER -