title: Functional roles of TRPV1 and TRPV4 in control of lower urinary tract activity: dual analysis of behavior and reflex during the micturition cycle.
abstract: The present study used a dual analysis of voiding behavior and reflex micturition to examine lower urinary tract function in transient receptor potential vanilloid (TRPV)1 knockout (KO) mice and TRPV4 KO mice. In metabolic cage experiments conducted under conscious conditions (i.e., voluntary voiding behavior), TRPV4 KO mice showed a markedly higher voiding frequency (VF; 19.3 ± 1.2 times/day) and a smaller urine volume/voiding (UVV; 114 ± 9 μl) compared with wild-type (WT) littermates (VF: 5.2 ± 0.5 times/day and UVV: 380 ± 34 μl). Meanwhile, TRPV1 KO mice showed a similar VF to WT littermates (6.8 ± 0.5 times/day) with a significantly smaller UVV (276 ± 20 μl). Water intake among these genotypes was the same, but TRPV4 KO mice had a larger urine output than the other two groups. In cystometrogram experiments conducted in decerebrate unanesthetized mice (i.e., reflex micturition response), no differences between the three groups were found in any cystometrogram variables, including voided volume, volume threshold for inducing micturition contraction, maximal voiding pressure, and bladder compliance. However, both TRPV1 KO and TRPV4 KO mice showed a significant number of nonvoiding bladder contractions (NVCs; 3.5 ± 0.9 and 2.8 ± 0.7 contractions, respectively) before each voiding, whereas WT mice showed virtually no NVCs. These results suggest that in the reflex micturition circuit, a lack of either channel is involved in NVCs during bladder filling, whereas in the forebrain, it is involved in the early timing of urine release, possibly in the conscious response to the bladder instability.
authors.affiliation: Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Yamanashi, Japan; PXN15164@nifty.ne.jp.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Yoshiyama
authors.affiliation: Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Yamanashi, Japan;
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Mochizuki
authors.affiliation: Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Yamanashi, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagomi
authors.affiliation: Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Yamanashi, Japan;
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Yamanashi, Japan;
authors.forename: Satoru
authors.initials: S
authors.lastname: Kira
authors.affiliation: Pharmacology Department, Nonclinical Research Center, Drug Development Service Segment, LSI Medience Corporation, Uto, Kumamoto, Japan;
authors.forename: Ryoji
authors.initials: R
authors.lastname: Mizumachi
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Aichi, Japan; and Department of Physiological Sciences, SOKENDAI (Graduate University for Advanced Studies), Okazaki, Aichi, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sokabe
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Aichi, Japan; and.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Takayama
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Aichi, Japan; and Department of Physiological Sciences, SOKENDAI (Graduate University for Advanced Studies), Okazaki, Aichi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Yamanashi, Japan;
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010641:Phenotype; D016548:Prosencephalon / Q000502:physiology; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001743:Urinary Bladder / Q000502:physiology; D014553:Urinary Tract Physiological Phenomena; D014554:Urination / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C486576:Trpv4 protein, mouse
keywords: bladder instability; central nervous system; forebrain; mouse; transient receptor potential vanilloid