Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.
Department of Urology, The 79th Army Hospital, 148 Weiguo Road, Baita District, Liaoyang, Liaoning, China.
Int Urol Nephrol. 2020 Oct;52(10):1851-1861. doi: 10.1007/s11255-020-02487-x. Epub 2020 May 12.
Overactive bladder (OAB) is related to detrusor overactivity (DO), which is caused by the increased detrusor smooth muscle (DSM) cells excitability. Small-conductance Ca-activated K (SK) channels is a fundamental regulator of excitability and contractility in DSM cells. Obesity-related OAB is associated with the decreased expression and regulatory function of SK channels in DSM layer. However, the regulation role of SK channels in obesity-related OAB DSM cell excitability is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM cells.
Female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. We performed urodynamic study, single-cell quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and patch-clamp electrophysiology.
Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. Single-cell qRT-PCR experiments discovered the decreased mRNA expression level of SK channel in DSM cell from HFD rats. Patch-clamp studies revealed that NS309, a SK channel activator, had an attenuated effect on membrane potential hyperpolarization in HFD DSM cells. In addition, the reduced whole cell SK channel currents were recorded in HFD DSM cells.
Attenuated SK channels expression and function, which results in the increased DSM cells excitability and contributes to DO, is discovered in obesity-related OAB DSM cells, suggesting that SK channels might be potential therapeutic targets to control OAB.
膀胱过度活动症（OAB）与逼尿肌过度活动（DO）有关，后者是由逼尿肌平滑肌（DSM）细胞兴奋性增加引起的。小电导钙激活钾（SK）通道是调节 DSM 细胞兴奋性和收缩性的基本调节因子。肥胖相关的 OAB 与 DSM 层中 SK 通道的表达和调节功能降低有关。然而，SK 通道在肥胖相关 OAB DSM 细胞兴奋性中的调节作用仍不清楚。在这里，我们检验了这样一个假设，即肥胖相关的 OAB 与 DSM 细胞中 SK 通道的表达和活性降低有关。
雌性 Sprague-Dawley 大鼠分别喂食正常饮食（ND）或高脂肪饮食（HFD），12 周后称重。我们进行尿动力学研究、单细胞定量逆转录聚合酶链反应（qRT-PCR）和膜片钳电生理学实验。
HFD 大鼠的平均体重增加和尿动力学表现出 OAB。单细胞 qRT-PCR 实验发现 HFD 大鼠 DSM 细胞中 SK 通道的 mRNA 表达水平降低。膜片钳研究显示，SK 通道激活剂 NS309 对 HFD DSM 细胞的膜电位超极化有减弱作用。此外，还记录到 HFD DSM 细胞的全细胞 SK 通道电流减少。
在肥胖相关的 OAB DSM 细胞中发现 SK 通道表达和功能减弱，导致 DSM 细胞兴奋性增加，促成 DO，提示 SK 通道可能是控制 OAB 的潜在治疗靶点。
