Fig. 8.

Schematic diagram illustrating the mechanisms by which M₃-R regulates BK channel function in rat DSM cells. Activation of M₃-Rs leads to IP₃ and diacylglycerol (DAG) production, via a pathway involving PLC and PIP₂. IP₃ activates IP₃-Rs, which releases Ca²⁺ from the SR. This IP₃-induced Ca²⁺ release transiently activates the BK channels. Over time, depletion of SR Ca²⁺ upon activation of M₃-Rs reduces Ca²⁺ spark activity, which leads to inhibition of STBKCs and depolarization of DSM cell RMP causing activation of VDCC, and thus increases DSM contractility. DAG activates PKC, which may lead to direct inhibition of the SR Ca²⁺ pump and RyRs resulting in suppression of Ca²⁺ sparks and STBKCs. Pharmacological tools used in this study to inhibit cellular sources of Ca²⁺ are indicated. DAG, diacylglycerol; PIP₂, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase-C; PLC, phospholipase-C; VDCC, L-type voltage-dependent Ca²⁺ channel.