Muscarinic stimulation of urinary bladder induces contraction via an increase in intracellular Ca(2+) concentration that results from Ca(2+) influx through Ca(2+) channels and/or IP(3)-mediated Ca(2+) release controlled by phospholipase C (PLC) signalling. The significance of PLC/IP(3) signalling in this cascade has recently been questioned because PLC inhibitors were without effect on carbachol-induced contractions in detrusor muscle strips. However, PLC/IP(3)-mediated Ca(2+) release was clearly observed in recordings of Ca(2+) signals in isolated myocytes. Therefore, we investigated the presence of PLC/IP(3)-dependent Ca(2+) release by directly monitoring Ca(2+) signals in intact detrusor muscle strips. Concomitant Ca(2+) signals from Ca(2+) channel activity were eliminated by the Ca(2+) channel antagonist isradipine (3 microM) or by the use of muscles from Ca(v)1.2 channel-deficient (SMACKO) mice. In absence of Ca(2+) channel activity, carbachol elicited contractions and Ca(2+) signals in muscles from wild type and SMACKO mice that were inhibited by the PLC inhibitor U73122 (10 microM). The results show that PLC/IP(3)-dependent Ca(2+) release is activated by stimulation with carbachol in urinary bladder smooth muscle but has a minor contribution to overall carbachol-induced Ca(2+) signals.     «

Muscarinic stimulation of urinary bladder induces contraction via an increase in intracellular Ca(2+) concentration that results from Ca(2+) influx through Ca(2+) channels and/or IP(3)-mediated Ca(2+) release controlled by phospholipase C (PLC) signalling. The significance of PLC/IP(3) signalling in this cascade has recently been questioned because PLC inhibitors were without effect on carbachol-induced contractions in detrusor muscle strips. However, PLC/IP(3)-mediated Ca(2+) release was clearl...     »