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Nicotinic acetylcholine receptors (nAChRs) are present in high density in insect nervous tissue and are targeted by neonicotinoid insecticides. Improved understanding of the actions of these insecticides will assist in the development of new compounds. Here, we have used whole-cell patch-clamp recording of cholinergic neurons cultured from the central nervous system of 3rd instar Drosophila larvae to examine the actions of acetylcholine (ACh) and nicotine, as well as the neonicotinoids imidacloprid, clothianidin and P-CH-clothianidin on native nAChRs of these neurons. Dose-response data yield an EC(50) value for ACh of 19 microm. Both nicotine and imidacloprid act as low efficacy agonists at native nAChRs, evoking maximal current amplitudes 10-14% of those observed for ACh. Conversely, clothianidin and P-CH-clothianidin evoke maximal current amplitudes up to 56% greater than those evoked by 100 microm ACh in the same neurons. This is the first demonstration of 'super' agonist actions of an insecticide on native insect nAChRs. Cell-attached recordings indicate that super agonism results from more frequent openings at the largest (63.5 pS) conductance state observed.

Original publication

DOI

10.1111/j.1471-4159.2006.04084.x

Type

Journal article

Journal

J Neurochem

Publication Date

10/2006

Volume

99

Pages

608 - 615

Keywords

Acetylcholine, Animals, Animals, Genetically Modified, Binding, Competitive, Cells, Cultured, Central Nervous System, Dose-Response Relationship, Drug, Drosophila melanogaster, Guanidines, Imidazoles, Insecticides, Larva, Membrane Potentials, Molecular Structure, Neurons, Nicotine, Nicotinic Agonists, Nitro Compounds, Patch-Clamp Techniques, Receptors, Nicotinic, Thiazoles