Modulation of the neuronal nicotinic acetylcholine receptor-channel by the nitromethylene heterocycle imidacloprid.

Nitromethylene heterocycle insecticides are known to act on the nicotinic acetylcholine receptor-channel. The effects of the nitromethylene heterocycle, imidacloprid, on the nicotinic acetylcholine receptor-channel of clonal rat phaeochromocytoma (PC12) cells were studied using whole-cell and single-channel patch clamp methods. Imidacloprid suppressed carbachol-induced whole-cell currents in a dose-dependent manner, and this compound itself generated small currents. Multiple conductance states of single-channel currents were also evoked by imidacloprid at the nicotinic acetylcholine receptor-channels. The most frequently generated single-channel currents showed two conductance states, 25.4 and 9.8 pS, which were identical to the conductance states of acetylcholine-generated currents. The mean open time and burst duration of the main conductance currents induced by imidacloprid were shorter than those induced by acetylcholine. Co-application of imidacloprid and acetylcholine caused some interactions at the two conductance states. Mean open time and mean burst duration of the main conductance state currents evoked by acetylcholine were decreased by the co-application of imidacloprid as compared with those induced by acetylcholine alone. In conclusion, imidacloprid has both multiple agonist and antagonist effects on the neuronal nicotinic acetylcholine receptor-channels.