Fig. 2. (A ) Lidocaine inhibits methylcholine (MCh) half-maximal effect concentration (EC50)-induced inward chloride current [ICl(Ca)] in a concentration-dependent manner. Curve fitting using the Hill equation revealed a half-maximal inhibitory concentration (IC50) of 1.8 ± 1.0 × 10−8m. (B ) Example trace of a MCh EC50-induced control response (top ) and ICl(Ca) after a 10-min treatment with lidocaine (10−7m) on a muscarinic response elicited by MCh EC50stimulation (bottom ). (C ) Responses induced by MCh (EC50) to determine the reversibility of lidocaine (10−3m) inhibition. Three consecutive measurements were made in each oocyte. First bar represents control response (8.5 ± 0.8 μC). The second bar shows the inhibitory effect of lidocaine. ICl(Ca)was reduced to 5% of control response (0.4 ± 0.3 μC). The third bar shows recovery after a 10-min Tyrode superfusion (6.8 ± 0.7 μC). There is no statistically significant difference between the control and recovery response (n.s.). (D ) Lidocaine acts primarily as a noncompetitive antagonist. Lidocaine did not shift the concentration–response curve for MCh to the right (4.2 ± 1.2 × 10−7m–6.8 ± 3.1 × 10−7m;P = 0.445, t test). Maximal effect (Emax) was significantly reduced after lidocaine administration (7.6 ± 0.3–4.4 ± 0.4 μC;P < 0.001, t test), making a noncompetitive antagonism most likely. (E ) Noncompetitive antagonism for lidocaine was confirmed by four consecutive measurements in the same oocyte. First bar represents control response elicited by stimulation of the oocyte using 1 μm MCh (5.1 ± 0.5 μC). The second bar shows the inhibitory effect of a 10-min superfusion with lidocaine (at approximately IC50 18 nm). One micromole per liter of MCh-induced ICl(Ca)was reduced to 54 ± 5.6% of control response. The third bar represents average response, again after a 10-min superfusion with lidocaine at approximately IC5018 nm, using 1 mm MCh as agonist. Average response size was reduced to 44.2 ± 3.2% of the control response (not significant to stimulation with 1 μm MCh, P > 0.05, repeated measurements analysis of variance, Turkey post hoc test). The fourth bar shows recovery after a 10-min Tyrode superfusion. ICl(Ca)was induced by administration of 1 μm MCh. Mean response size recovered to 89.3 ± 4.3% of the control response (not significant to control response, P > 0.05, repeated measurements analysis of variance, Turkey post hoc test).