Evaluation of mouse urinary bladder smooth muscle for diurnal differences in contractile properties.
Evaluation of mouse urinary bladder smooth muscle for diurnal differences in contractile properties.
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DOI：
10.3389/fphar.2014.00293
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发表时间：
2014
影响因子：
5.6
通讯作者：
Meredith AL
中科院分区：
文献类型：
--
作者：
White RS;Zemen BG;Khan Z;Montgomery JR;Herrera GM;Meredith AL
大多数生理系统表现出功能输出的日常变化，伴随着昼夜周期。人类表现出每日排尿节律（排尿），这种节律的破坏（夜尿）具有显着的临床影响。然而，其基本机制尚不清楚。最近，在啮齿动物中证明了排尿的昼夜节律与尿动力学的功能变化相关，为在动物模型中解决这个问题提供了机会。来自小鼠膀胱的平滑肌细胞已被提议在分子水平上表达功能性和自主的生物钟。在这项研究中，我们探讨了小鼠膀胱平滑肌（UBSM）的半完整制剂是否在白天和夜间表现出可测量的收缩性差异。在昼夜周期的四个时间点收获 UBSM 组织条，并使用等长张力记录评估自发（阶段性）收缩和神经诱发收缩。在啮齿类动物排尿频率较高的活动期 (ZT12-24) 期间，与从休息期 (ZT0-12) 收获的试纸条相比，UBSM 试纸条在最大（高 K+）或神经诱发收缩方面没有显着差异。然而，观察到阶段性收缩的昼夜节律，ZT10 处的振幅较高。与增强的相位幅度一致，BK K+通道（UBSM兴奋性的关键抑制因子）的表达在ZT8处较低。 ZT20 处 BK 的较高表达与 BK 拮抗剂 paxilline (PAX) 对相位幅度的增强作用相关，但 PAX 对相位频率或神经诱发的收缩没有显着的时间依赖性影响。总体而言，这些结果确定了膀胱肌的一项收缩参数的昼夜差异。总而言之，结果表明 UBSM 中的自主时钟对昼夜排尿模式的综合控制贡献有限。
Most physiological systems show daily variations in functional output, entrained to the day–night cycle. Humans exhibit a daily rhythm in urinary voiding (micturition), and disruption of this rhythm (nocturia) has significant clinical impact. However, the underlying mechanisms are not well-understood. Recently, a circadian rhythm in micturition was demonstrated in rodents, correlated with functional changes in urodynamics, providing the opportunity to address this issue in an animal model. Smooth muscle cells from mouse bladder have been proposed to express a functional and autonomous circadian clock at the molecular level. In this study, we addressed whether a semi-intact preparation of mouse urinary bladder smooth muscle (UBSM) exhibited measurable differences in contractility between day and night. UBSM tissue strips were harvested at four time points over the diurnal cycle, and spontaneous (phasic) and nerve-evoked contractions were assessed using isometric tension recordings. During the active period (ZT12-24) when micturition frequency is higher in rodents, UBSM strips had no significant differences in maximal- (high K+) or nerve-evoked contractions compared to strips harvested from the resting period (ZT0-12). However, a diurnal rhythm in phasic contraction was observed, with higher amplitudes at ZT10. Consistent with the enhanced phasic amplitudes, expression of the BK K+ channel, a key suppressor of UBSM excitability, was lower at ZT8. Higher expression of BK at ZT20 was correlated with an enhanced effect of the BK antagonist paxilline (PAX) on phasic amplitude, but PAX had no significant time-of-day dependent effect on phasic frequency or nerve-evoked contractions. Overall, these results identify a diurnal difference for one contractile parameter of bladder muscle. Taken together, the results suggest that autonomous clocks in UBSM make only a limited contribution to the integrated control of diurnal micturition patterns.