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

BACKGROUND AND PURPOSE The acute effects of PGE sub(2) on bladder smooth muscle and nerves were examined to determine the origin of PGE sub(2)-induced spontaneous rhythmic contractions. EXPERIMENTAL APPROACH Contraction studies, confocal Ca super(2+) imaging and electrophysiological recordings in strips of mouse urinary bladder were used to differentiate the effects of PGE sub(2) on bladder smooth muscle and efferent nerves. KEY RESULTS PGE sub(2) (50 mu M) increased the tone and caused phasic contractions of detrusor smooth muscle strips. Confocal Ca super(2+) imaging showed that PGE sub(2) increased the frequency of whole-cell Ca super(2+) transients (WCTs) (72 plus or minus 5%) and intracellular recordings showed it increased the frequency of spontaneous depolarizations, from 0.31.s super(-1) to 0.90.s super(-1). Non-selective inhibition of EP receptors using SC-51322 and AH-6809 (10 mu M), or the L-type Ca super(2+) channel blocker nifedipine (1 mu M), prevented these phasic contractions and WCTs, and reduced the tone (by 45 plus or minus 7% and 59 plus or minus 6%, respectively). Blocking P2X1 receptors with NF449 (10 mu M) caused a small but significant reduction in the frequency of PGE sub(2)-induced phasic contractions (24 plus or minus 9%) and WCTs (28 plus or minus 17%) but had no significant effect on spontaneous depolarizations or tone. Inhibiting muscarinic receptors with cyclopentolate (1 mu M) had no significant effect on these measures. Spontaneous WCTs became synchronous in PGE sub(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 sub(2) to increase detrusor spontaneous rhythmic activity does not require parasympathetic nerves.