Ridlon Monica, Tlapa Julia, Stietz Kimberly Keil
Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 Linden Dr, Madison, WI, 53706, USA.
J Muscle Res Cell Motil. 2025 Sep 1. doi: 10.1007/s10974-025-09707-w.
In the lower urinary tract, coordinated function between the bladder and urethra is essential for normal micturition, requiring smooth muscle contraction and relaxation in a tightly regulated cycle. During the bladder filling phase, the bladder remains relaxed while the urethra stays contracted to prevent leakage. During voiding, this coordination reverses, and the bladder contracts to expel urine while the relaxed urethra allows urine flow. These functions are essential for proper micturition and two key molecular regulators of this process are the large-conductance calcium activated potassium (BK) channels and ryanodine receptors (RyRs), both of which modulate smooth muscle excitability and calcium dynamics. This review provides an overview of the roles of BK channels and RyR mediated signaling in regulating smooth muscle activity in the bladder and urethra, with a focus on their contributions to lower urinary tract physiology and pathophysiology. BK channels act as negative feedback modulators, dampening myogenic and nerve-evoked contractions of the detrusor and urethra. RyRs play a role in regulating intracellular calcium signaling that supports both muscle relaxation and contraction. This review highlights alterations in the function of these channels in lower urinary tract dysfunction, and as potential targets for other factors such as environmental exposures to disrupt voiding function. BK channels and RyRs are plausible targets for therapeutic strategies aimed at improving bladder and urethra function in certain patients, particularly those with lower urinary tract symptoms caused by factors such as aging and environmental chemical exposure.
在下尿路中，膀胱和尿道之间的协调功能对于正常排尿至关重要，这需要平滑肌在严格调控的周期中进行收缩和舒张。在膀胱充盈期，膀胱保持舒张状态，而尿道则保持收缩以防止漏尿。在排尿时，这种协调关系逆转，膀胱收缩以排出尿液，而舒张的尿道则允许尿液流出。这些功能对于正常排尿至关重要，而这一过程的两个关键分子调节因子是大电导钙激活钾（BK）通道和兰尼碱受体（RyR），它们都能调节平滑肌的兴奋性和钙动力学。本综述概述了BK通道和RyR介导的信号传导在调节膀胱和尿道平滑肌活动中的作用，重点关注它们对下尿路生理和病理生理的贡献。BK通道作为负反馈调节因子，可抑制逼尿肌和尿道的肌源性及神经诱发的收缩。RyR在调节支持肌肉舒张和收缩的细胞内钙信号传导中发挥作用。本综述强调了这些通道功能在下尿路功能障碍中的改变，以及作为环境暴露等其他因素破坏排尿功能的潜在靶点。BK通道和RyR是旨在改善某些患者膀胱和尿道功能的治疗策略的合理靶点，尤其是那些由衰老和环境化学暴露等因素引起下尿路症状的患者。
