Distinct roles of M1 and M3 muscarinic acetylcholine receptors controlling oscillatory and non-oscillatory [Ca2+]i increase

We examined ACh-induced [Ca2+](i) dynamics in pancreatic acinar cells prepared from mAChR subtype-specific knockout (KO) mice. ACh did not induce any [Ca2+](i) increase in the cells isolated from M1/M3 double KO mice. In the cells from M3KO mice, ACh (0.3-3 mu M) caused a monotonic [Ca2+](i) increase. However, we found characteristic oscillatory [Ca2+](i) increases in cells from M1KO mice in lower concentrations of ACh (0.03-0.31 mu M). We investigated the receptor specific pattern of [Ca2+](i) increase in COS-7 cells transfected with M1 or M3 receptors. ACh induced the oscillatory [Ca2+](i) increase in M3 expressing cells, but not in cells expressing M1, which exhibited monotonic [Ca2+](i), increases. IP3 production detected in fluorescent indicator co-transfected cells was higher in M1 than in M3 expressing cells. From the examination of four types of M1/M3 chimera receptors we found that the carboxyl-terminal region of M3 was responsible for the generation of Ca2+ oscillations. The present results suggest that the oscillatory Ca2+ increase in response to M3 stimulation is dependent upon a moderate IP3 increase, which is suitable for causing Ca2+-dependent IP3-induced Ca2+ release. The C-terminal domain of M3 may contribute as a regulator of the efficiency of Gq and PLC cooperation. (C) 2013 Elsevier Ltd. All rights reserved.