Figure 3. Pathways for M-channel activation and inhibition.

A, channels are normally activated by membrane PIP₂. B, muscarinic receptor stimulation closes M-channels by reducing membrane PIP₂. C, bradykinin closes channels through IP₃-mediated Ca²⁺ release. D, when Ca²⁺ release is suppressed and PIP₂ synthesis blocked, bradykinin can instead close channels by reducing PIP₂. Abbreviations: PI, phosphatidylinositol; PIP, phosphatidylinositol-4-phosphate; PIP₂, phosphatidylinositol-4,5-bisphosphate (PI(4,5)P₂); PI(4)-K, phosphatidylinositol-4-kinase; PI4(5)-K, phosphatidylinositol-4-phosphate; Oxo-M, oxotremorine-M; M1-mAChR, M1 muscarinic acetylcholine receptor; Gαq, α-subunit of the G proteins Gq; Gαq/11, α-subunit of the G proteins Gq and/or G11; PLC, phospholipase-C; PLCβ4, phospholipase-C β4; DAG, diacylglycerol; IP₃, inositol-1,4,5-trisphosphate; BK, bradykinin; B2-BKR, B2-bradykinin receptor; CaM, calmodulin; WM, wortmannin; thaps, thapsigargin. See text for further details. (Adapted from Hughes et al. (2007), with permission.)