Ca²⁺ Sparks and K_Ca Channels: Novel Mechanisms to Relax Urinary Bladder Smooth Muscle

Abstract

The urinary bladder is a unique organ that must able to relax while filling with urine and contract forcefully to expel urine during micturition. Micturition is under voluntary control, and involves the synchronized contraction of smooth muscle cells in the bladder wall.³ During filling, the urinary bladder maintains a relatively constant internal pressure as the bladder wall expands. To achieve this, smooth muscle cells in the bladder wall must simultaneously maintain tension and gradually increase in length as the bladder wall thins and stretches. Despite the central role in bladder physiology, mechanisms underlying this modulation of excitation-contraction coupling are poorly understood. Previous findings from our laboratory and others have shown that calcium-activated K⁺ (K_Ca) channels play a prominent role in the regulation of urinary bladder smooth muscle (UBSM) contractility. In this study, we explore the modulation of excitation-contraction coupling by ryanodine receptors (RyRs) and K_Ca channels. To understand the complex interplay between RyRs and K_Ca channels, we used a multifaceted approach that includes molecular techniques, electrophysiology, force measurements, and rapid calcium imaging. Elucidating mechanisms that control UBSM relaxation will increase our understanding of both normal and dysfunctional urinary bladder physiology, and ultimately lead to the development of therapeutics to control certain forms of urinary incontinence.