Functional roles of TRPV1 and TRPV4 in control of lower urinary tract activity: dual analysis of behavior and reflex during the micturition cycle
Functional roles of TRPV1 and TRPV4 in control of lower urinary tract activity: dual analysis of behavior and reflex during the micturition cycle
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DOI：
10.1152/ajprenal.00016.2015
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发表时间：
2015-05-15
影响因子：
4.2
通讯作者：
Takeda, Masayuki
中科院分区：
文献类型：
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作者：
Yoshiyama, Mitsuharu;Mochizuki, Tsutomu;Takeda, Masayuki
本研究采用排尿行为和反射排尿的双重分析来检查瞬时受体电位香草酸（TRPV）1敲除（KO）小鼠和TRPV 4敲除小鼠的下尿路功能。在有意识条件下进行的代谢笼实验中（即，自发排尿行为），与野生型（WT）同窝小鼠（VF：5.2 +/-0.5次/天和UVV：380 +/-34 μ l）相比，TRPV 4 KO小鼠显示出明显更高的排尿频率（VF：19.3 +/-1.2次/天）和更小的尿量/排尿（UVV：114 +/-9 μ l）。同时，TRPV 1 KO小鼠显示出与WT同窝小鼠相似的VF（6.8 +/- 0.5次/天），具有显著较小的UVV（276 +/- 20 μ l）。这些基因型之间的水摄入量是相同的，但TRPV 4 KO小鼠的尿量比其他两组更大。在去大脑未麻醉小鼠（即，反射性排尿反应），三组之间的任何膀胱测压变量均无差异，包括排尿量、诱发排尿收缩的容量阈值、最大排尿压和膀胱顺应性。然而，TRPV 1 KO和TRPV 4 KO小鼠在每次排尿前均显示出显著数量的非排尿性膀胱收缩（NVC;分别为3.5 +/- 0.9和2.8 +/- 0.7收缩），而WT小鼠几乎没有显示出NVC。这些结果表明，在反射排尿回路中，缺乏任何通道参与膀胱充盈期间的NVC，而在前脑中，它参与尿液释放的早期定时，可能在有意识的反应膀胱不稳定。
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 mu l) compared with wild-type (WT) littermates (VF: 5.2 +/- 0.5 times/day and UVV: 380 +/- 34 mu l). Meanwhile, TRPV1 KO mice showed a similar VF to WT littermates (6.8 +/- 0.5 times/day) with a significantly smaller UVV (276 +/- 20 mu l). 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.