Fig. 3.

Agonist pharmacology of the L-AChR. (A) (Left) Acetylcholine, levamisole, and pyrantel, but not nicotine, activate the L-AChR. Concentrations of agonist are indicated above each application. Traces are from a single oocyte. (Right) Current relative to 100 μM ACh (plateau values): 100 μM levamisole 38 ± 6% (n = 6), 100 μM pyrantel 6.1 ± 0.7% (n = 6), 500 μM nicotine 0.55 ± 0.21% (n = 4). (B) Dose–response curves for ACh and levamisole. The value at 500 μM levamisole has been excluded from the fit because of voltage-dependent block at this concentration. (C) High concentrations of levamisole cause voltage-dependent channel block of L-AChR. BAPTA-injected oocytes were subjected to voltage ramps in the presence of 100 μM or 500 μM levamisole (n = 5). (Inset) Representative traces of L-AChR responses evoked by 100 μM and 500 μM levamisole. The rebound of the current after washout of 500 μM levamisole probably occurs because unbinding of levamisole from its pore-blocking site is faster than unbinding of levamisole from its agonist site. (D) Concentration-dependent washout kinetics of levamisole-evoked responses. ACh or levamisole traces obtained from a single oocyte at different agonist concentrations were first normalized to the current level measured just before agonist washout and then superimposed. Note that although ACh-evoked responses display classical concentration-independent washout kinetics, the washout time course of levamisole-evoked responses increases with increasing levamisole concentrations.