Phospholipase C mediated Ca signals in murine urinary bladder smooth muscle

Muscarinic stimulation of urinary bladder induces contraction via an increase in intracellular Ca²⁺ concentration that results from Ca²⁺ influx through Ca²⁺ channels and/or IP₃-mediated Ca²⁺ release controlled by phospholipase C (PLC) signalling. The significance of PLC/IP₃ signalling in this cascade has recently been questioned because PLC inhibitors were without effect on carbachol-induced contractions in detrusor muscle strips. However, PLC/IP₃-mediated Ca²⁺ release was clearly observed in recordings of Ca²⁺ signals in isolated myocytes. Therefore, we investigated the presence of PLC/IP₃-dependent Ca²⁺ release by directly monitoring Ca²⁺ signals in intact detrusor muscle strips. Concomitant Ca²⁺ signals from Ca²⁺ channel activity were eliminated by the Ca²⁺ channel antagonist isradipine (3 µM) or by the use of muscles from Ca_v1.2 channel-deficient (SMACKO) mice. In absence of Ca²⁺ channel activity, carbachol elicited contractions and Ca²⁺ signals in muscles from wild type and SMACKO mice that were inhibited by the PLC inhibitor U73122 (10 µM). The results show that PLC/IP₃-dependent Ca²⁺ release is activated by stimulation with carbachol in urinary bladder smooth muscle but has a minor contribution to overall carbachol-induced Ca²⁺ signals.