Effects of nitenpyram on the neuronal nicotinic acetylcholine receptor-channel in rat phaeochromocytoma PC12 cells

Nitenpyram, (E)-N-(6-chloro-3-pyridylmethyl)-N-ethyl-N'-methyl-2-nitro-viny lidenediamine is known to act on the nicotinic acetylcholine receptor-chann el (AChR). We examined the effects of nitenpyram on the neuronal type of th e nicotinic AChR in rat clonal phaeochromocytoma PC12 cells using a patch c lamp technique to clarify the mechanisms of action at the single-channel le vel. Nitenpyram itself induced single-channel currents mediated by the neur onal nicotinic AChR. Go-application of ACh and nitenpyram opened the channe ls exhibiting the two conductance states. The proportion of main conductanc e levels was decreased and that of subconductance levels was increased in t he 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 cur rent. These changes of single-channel kinetics result in a decrease in prob ability of openings of main conductance state currents explaining the effec ts of nitenpyram on the neuronal nicotinic AChR. The effects of nitenpyram on the acetylcholine-induced current are deemed directly responsible for th e toxic actions in animals.