Desensitization of nicotinic acetylcholine receptors in central nervous system neurons of the stick insect (Carausius morosus) by imidacloprid and sulfoximine insecticides

Imidacloprid, sulfoxaflor and two experimental sulfoximine insecticides caused generally depressive symptoms in stick insects, characterized by stillness and weakness, while also variably inducing postural changes such as persistent ovipositor opening, leg flexion or extension and abdomen bending that could indicate excitation of certain neural circuits. We examined the same compounds on nicotinic acetylcholine receptors in stick insect neurons, which have previously been shown to desensitize in the presence of ACh. Brief U-tube application of 10−4 M solutions of insecticides for 1 s evoked currents that were much smaller than ACh-evoked currents, and depressed subsequent ACh-evoked currents for several minutes, indicating that the compounds are low-efficacy partial agonists that potently desensitize the receptors. Much lower concentrations of insecticides applied in the bath for longer periods did not activate currents, but inhibited ACh-evoked currents via desensitization of the receptors. Previously described fast- and slowly-desensitizing nACh currents, IACh1 and IACh2 respectively, were each found to consist of two components with differing sensitivities to the insecticides. Imidacloprid applied in the bath desensitized high-sensitivity components, IACh1H and IACh2H with IC50s of 0.18 and 0.13 pM, respectively. It desensitized the low-sensitivity slowly desensitizing component, IACh2L, with an IC50 of 2.6 nM, while a component of the fast-desensitizing current, IACh1L, was least sensitive, with an IC50 of 81 nM IACh1L appeared to be insensitive to the three sulfoximines tested, whereas all three sulfoximines potently desensitized IACh1H and both slowly desensitizing components, with IC50s between 2 and 7 nM. We conclude that selective desensitization of certain nAChR subtypes can account for the insecticidal actions of imidacloprid and sulfoximines in stick insects.

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► IACh in stick insect neurons can be resolved into four desensitizing components.
► Imidacloprid and sulfoximines are partial agonists that potently desensitize 3 of 4 IACh components.
► An IACh component with low imidacloprid (IMI) sensitivity was sulfoximine-insensitive.
► Sulfoximines, like IMI, appear to work by desensitization of certain nAChR subtypes.