Effects of Nitenpyram on the Neuronal Nicotinic Acetylcholine Receptor-Channel in Rat Phaeochromocytoma PC12 Cells

Abstract

Nitenpyram, (E)-N-(6-chloro-3-pyridylmethyl)-N-ethyl-N'-methyl-2-nitro-vinylidenediamine, is known to act on the nicotinic acetylcholine receptor-channel (AChR). We examined the effects of nitenpyram on the neuronal type of the nicotinic AChR in rat clonal phaeochromocytoma PC12 cells using a patch clamp technique to clarify the mechanisms of action at the single-channel level. Nitenpyram itself induced single-channel currents mediated by the neuronal nicotinic AChR. Co-application of ACh and nitenpyram opened the channels exhibiting the two conductance states. The proportion of main conductance levels was decreased and that of subconductance levels was increased in the presence of nitenpyram. The open time and closed time distribution, but not for the burst duration, for the main conductance state currents with co-application of ACh and nitenpyram were similar to those of ACh-induced current. These changes of single-channel kinetics result in a decrease in probability of openings of main conductance state currents explaining the effects of nitenpyram on the neuronal nicotinic AChR. The effects of nitenpyram on the acetylcholine-induced current are deemed directly responsible for the toxic actions in animals.