Afferent Activity is Greatly Increased by Spontaneous Phasic Contractions in Mouse Ex Vivo Urinary Bladder

Abstract

Spontaneous phasic contractions (SPCs) are transient, non‐voiding contractions during urinary bladder filling that hallmark many bladder pathologies. However, the origin and physiological importance of SPCs are largely unknown. Using an ex vivo mouse urinary bladder preparation, we examined the relationship between SPCs and afferent nerve activity. Continuous bladder filling (30 µl/min) alone increased baseline afferent activity (~100 Hz per 4 mmHg pressure). Strikingly, over the same pressure range, SPCs evoked bursts of afferent activity that were more than 3‐fold greater than baseline afferent activity (>350 Hz) and often contained large‐amplitude action potentials not normally observed in the absence of SPCs. The frequency of afferent bursts correlated with the SPC rate of rise, and peaked prior to the associated SPC. Inhibition of neuronal Na+ channels blocked afferent nerve activity without altering SPC amplitude, duration or rate of rise. In contrast, inhibition of smooth muscle voltage‐dependent Ca2+ channels (VDCCs) abolished SPCs as well as all associated afferent bursts, indicating afferent bursts coupled directly to the smooth muscle contractile machinery. However, In the presence of VDCC blockers, mechanical deformation of the bladder evoked SPC‐like events and afferent bursts with an amplitude and SPC/afferent ratio typical of “natural” SPCs. This supports the concept that mechanical distention of the bladder by SPCs generates bursts of sensory nerve activity that dominate bladder afferent outflow. These findings suggest that SPC‐dependent bursts of afferent activity may convey sensory information about bladder fullness to the CNS, and thus contribute to the regulation of micturition frequency. Supported by NIH R37DK053832.