Fig. 4. Cholinergic modulation of sevoflurane effects on network activity in cortical and spinal slices. ( A ) Acetylcholine augmented neuronal firing rates in cortical slices at all sevoflurane concentrations tested, causing a concentration-dependent rightward and upward shift of the sevoflurane concentration–response curve. ( B ) In spinal slices, 10 μm acetylcholine produced a less pronounced increase in action potential activity. ( C ) Cholinergic modulation of normalized data of action potential activity depressed by sevoflurane in cortical slices. Acetylcholine increased the EC50from 0.83 ± 0.03 MAC (1 MAC is defined to be the minimum alveolar concentration of an inhaled anesthetic required to suppress movement in response to noxious stimulation in 50% of subjects) in the absence of acetylcholine to 1.59 ± 0.32 MAC (1 μm acetylcholine) and 2.68 ± 0.57 MAC (10 μm acetylcholine). The concentration–response curves of sevoflurane measured in the presence of acetylcholine differed significantly from the concentration–response curve in the absence of acetylcholine ( P < 0.001, F test). ( D ) Acetylcholine did not reduce the potency of sevoflurane in depressing spinal neurons (0.49 ± 0.05 MAC in the absence compared with 0.47 ± 0.10 MAC in the presence of acetylcholine). The concentration–response curves did not differ significantly ( P > 0.1, F test).