Prostaglandin E 2 induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves

BACKGROUND AND PURPOSE The acute effects of PGE 2 on bladder smooth muscle and nerves were examined to determine the origin of PGE 2 ‐induced spontaneous rhythmic contractions. EXPERIMENTAL APPROACH Contraction studies, confocal Ca 2+ imaging and electrophysiological recordings in strips of mouse urinary bladder were used to differentiate the effects of PGE 2 on bladder smooth muscle and efferent nerves. KEY RESULTS PGE 2 (50 µM) increased the tone and caused phasic contractions of detrusor smooth muscle strips. Confocal Ca 2+ imaging showed that PGE 2 increased the frequency of whole‐cell Ca 2+ transients (WCTs) (72 ± 5%) and intracellular recordings showed it increased the frequency of spontaneous depolarizations, from 0.31·s −1 to 0.90·s −1 . Non‐selective inhibition of EP receptors using SC‐51322 and AH‐6809 (10 µM), or the L‐type Ca 2+ channel blocker nifedipine (1 µM), prevented these phasic contractions and WCTs, and reduced the tone (by 45 ± 7% and 59 ± 6%, respectively). Blocking P2X1 receptors with NF449 (10 µM) caused a small but significant reduction in the frequency of PGE 2 ‐induced phasic contractions (24 ± 9%) and WCTs (28 ± 17%) but had no significant effect on spontaneous depolarizations or tone. Inhibiting muscarinic receptors with cyclopentolate (1 µM) had no significant effect on these measures. Spontaneous WCTs became synchronous in PGE 2 , implying enhanced functional coupling between neighbouring cells. However, the electrical input resistance was unchanged. CONCLUSIONS AND IMPLICATIONS It was concluded that depolarization alone is sufficient to explain a functional increase in intercellular coupling and the ability of PGE 2 to increase detrusor spontaneous rhythmic activity does not require parasympathetic nerves.