Diurnal Variation in Mouse Urinary Bladder Smooth Muscle (UBSM) Contractility

Abstract

Physiological output varies by time of day, coordinated by the central circadian clock in the hypothalamus. Recently, a circadian rhythm in micturition was demonstrated in rodents, correlated with a day‐night change in the storage and voiding of the bladder. The goal of this study was to determine whether isolated UBSM exhibited an intrinsic difference in contractility between day and night. Mouse UBSM strips were harvested at 4 time points over the circadian cycle, zeitgeber time (ZT) 2, 8, 14, and 20, and phasic and nerve‐evoked (EFS) contractions were investigated using isometric tension recordings. We hypothesized that UBSM harvested from mice during the active period when micturition peaks (ZT8–14) would demonstrate stronger contractile activity than strips harvested during the rest period (ZT20–2), when the bladder relaxes to store urine. Compared to ZT20, at ZT8 UBSM strips exhibited larger KCl‐induced (10 ± 0.4 versus 7 ± 0.4 mN), phasic (0.08 ± 0.02 versus 0.03 ± 0.01 mN), and EFS‐induced contractions (28 ± 3 versus 22 ± 2 mN, n = 6 mice per condition). Increased contractile amplitudes at ZT8 were correlated with lower expression of the BK K+ channel, a regulator of UBSM excitability. These results identify a diurnal difference in UBSM contractility in the absence of central control, and suggest that daily regulation of bladder excitability occurs locally within smooth muscle tissue. Funded by NIDDK R21089337.