Smooth muscle of the lower urinary tract: BK-RyR coupling in physiology and pathophysiology

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.