Modulation of the Neuronal Nicotinic Acetylcholine Receptor Channel by Imidacloprid and Cartap

Abstract

Imidacloprid, a nitromethylene heterocycle insecticide, and cartap, a synthetic analog of nereistoxin, are known to act on the nicotinic acetylcholine receptor channel. The effects of imidacloprid and cartap on the nicotinic acetylcholine receptor channel of clonal rat phaeochromocytoma cells were studied using the single-channel patch-clamp technique. Acetylcholine at a concentration of 10 μM induced currents predominantly in the main conductance state, whereas imidacloprid at 10 μM induced currents predominantly in the subconductance state. No current was evoked by cartap at concentrations ranging from 0.1 to 300 μM. Coapplication of acetylcholine and imidacloprid generated currents in both main conductance state and subconductance state. Coapplication of acetylcholine and cartap induced the main conductance state currents, forming bursts. The distributions of open time and burst duration of currents induced by acetylcholine, imidacloprid, acetylcholine plus imidacloprid, and acetylcholine plus cartap showed multiexponential components. Cartap, when coapplied with acetylcholine, markedly shortened the open time reflecting the appearance of bursts. These results indicate that imidacloprid and cartap modulate the nicotinic acetylcholine receptor channel with different mechanisms of action. Imidacloprid acts as a partial agonist generating predominantly subconductance state currents, whereas cartap acts as an open channel blocker at the nicotinic acetylcholine receptor channel.