Fig. 11. A hypothetical scheme of the effects of local anesthetics on muscarinic receptor–mediated extracellular signal-regulated kinases (ERKs) in PC12 cells. The stimulation of muscarinic receptors in the cellular membranes initiates a sequence of activation of protein kinase C, Ras, Raf, and mitogen-activated protein kinase (MEK) that in turn activates ERKs. Local anesthetics perturb the cascade of the m3AChR-mediated ERK activation. In addition, the action of local anesthetics is independent of their effects on the voltage-dependent Na+channels. Inhibition of Na+–K+pumps does not affect the muscarinic acetylcholine receptor–mediated ERK activation.