Prostaglandin E2 modulates contractility of mouse bladder smooth muscle cells

Prostaglandin E2 (PGE₂) is an important local mediator in the urinary bladder, where it contributes to the regulation of detrusor excitability and is implicated in pathological conditions such as overactive bladder. Although previous studies have shown that exogenous PGE enhances bladder contractile activity, its effects on calcium signaling in individual detrusor smooth muscle cells (SMCs) and its interaction with cholinergic stimulation remain incompletely understood.

Acute detrusor tissue slices were prepared from adult female NMRI mice and loaded with the calcium indicator Calbryte 520 AM. Confocal calcium imaging was used to quantify spontaneous and stimulated intracellular Ca²⁺ activity in individual SMCs. The effects of PGE₂ alone and in combination with increasing concentrations of carbachol (CCh) were assessed by measuring oscillation active time, frequency, and duration of Ca²⁺ events. Tissue contractions were evaluated by visual inspection of image sequences.

PGE₂ increased spontaneous Ca²⁺ activity in detrusor SMCs, as reflected by a significant increase in active time due to increases in oscillation frequency, while oscillation duration remained unchanged. PGE₂ also recruited additional SMCs into an active state and induced localized tissue contractions. In the presence of PGE₂, lower concentrations of CCh evoked greater Ca²⁺ activity than under control conditions, suggesting that PGE₂ increased baseline detrusor excitability and reduced the additional cholinergic input required to evoke detectable Ca²⁺ activity. This effect was again mediated predominantly by an increase in oscillation frequency rather than duration. At the tissue level, PGE₂ enhanced CCh-induced contractility and shifted generalized contractions to lower CCh concentrations.

PGE₂ acts as a local excitatory modulator of mouse detrusor smooth muscle, increasing spontaneous Ca²⁺ activity and sensitizing the tissue to cholinergic stimulation. These effects are associated primarily with frequency-based modulation of Ca²⁺ oscillations and may represent a cellular mechanism contributing to detrusor overactivity under conditions of increased prostaglandin signaling.