Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding
Thomas Gevaert, Joris Vriens, Andrei Segal, Wouter Everaerts, Tania Roskams, Karel Talavera, Grzegorz Owsianik, Wolfgang Liedtke, Dirk Daelemans, Ilse Dewachter, Fred Van Leuven, Thomas Voets, Dirk De Ridder, Bernd Nilius
Thomas Gevaert, Joris Vriens, Andrei Segal, Wouter Everaerts, Tania Roskams, Karel Talavera, Grzegorz Owsianik, Wolfgang Liedtke, Dirk Daelemans, Ilse Dewachter, Fred Van Leuven, Thomas Voets, Dirk De Ridder, Bernd Nilius
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Research Article Nephrology

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 4α-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

Thomas Gevaert, Joris Vriens, Andrei Segal, Wouter Everaerts, Tania Roskams, Karel Talavera, Grzegorz Owsianik, Wolfgang Liedtke, Dirk Daelemans, Ilse Dewachter, Fred Van Leuven, Thomas Voets, Dirk De Ridder, Bernd Nilius

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Figure 3

Spontaneous voiding pattern of unrestrained TRPV4+/+ and TRPV4–/– mice.

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Spontaneous voiding pattern of unrestrained TRPV4+/+ and TRPV4–/– mice. ...
Photographs of filter papers taken out from the bottom cages containing single TRPV4+/+ (A) or TRPV4–/–mice (B) for 24 hours. Under ultra­violet light, urine spots are distinguished from the blue background by their lighter or yellowish color. Arrows labeled a, b, and c point to areas and voiding volumes of 0.22 cm2 (2.75 μl), 1.6 cm2 (20 μl), and 3.4 cm2 (42.5 μl), respectively. (C and D) Normalized probability density functions (pdf) of finding urine spots along the x and y axes of the cage for TRPV4+/+ (black lines) and TRPV4–/– (red lines) mice. (E) Average total spot area expressed as percentage of the total area of the cage. (F) Mean total number of spots and mean number of spots appearing away from the cage corners (out-of-corner). (G) Cumulative distribution functions (Cdf) for the area and volume of voiding for clearly discernible single spots (occurring away from the cage corners). The black square and the red circle indicate the mean values of the single-spot area and voiding volume for TRPV4+/+ and TRPV4–/– mice, respectively. Data from 14 TRPV+/+ mice and 23 TRPV4–/– mice. All data are mean ± SEM, by Student’s t test. *P < 0.05.