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NEUROPHARMACOLOGY

Calcium-Activated Potassium Channels in Insect Pacemaker Neurons as Unexpected Target Site for the Novel Fumigant Dimethyl Disulfide

Laboratoire Récepteurs et Canaux Ioniques Membranaires Unité Propre de Recherche et de l'Enseignement Supérieur, Equipe d'Accueil 2647/Unité Sous Contrat Institut National de la Recherche Agronomique, Université d'Angers, Unité de Formation et de Recherche Sciences, Angers cedex, France (H.G., C.L., B.L.); and Institut de Recherche sur la Biologie de l'Insecte, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6035, Université François Rabelais, Faculté des Sciences, Parc de Grandmont, France (J.A.)

Dimethyl disulfide (DMDS), a plant-derived insecticide, is a promising fumigant as a substitute for methyl bromide. To further understand the mode of action of DMDS, we examined its effect on cockroach octopaminergic neurosecretory cells, called dorsal unpaired median (DUM) neurons, using whole-cell patch-clamp technique, calcium imaging and antisense oligonucleotide strategy. At low concentration (1 µM), DMDS modified spontaneous regular spike discharge into clear bursting activity associated with a decrease of the amplitude of the afterhyperpolarization. This effect led us to suspect alterations of calcium-activated potassium currents (IKCa) and [Ca²⁺]_i changes. We showed that DMDS reduced amplitudes of both peak transient and sustained components of the total potassium current. IKCa was confirmed as a target of DMDS by using iberiotoxin, cadmium chloride, and pSlo antisense oligonucleotide. In addition, we showed that DMDS induced [Ca²⁺]_i rise in Fura-2-loaded DUM neurons. Using calcium-free solution, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxy-phenyl)ethyl]-acetamide (LOE 908) [an inhibitor of transient receptor potential (TRP)], we demonstrated that TRP initiated calcium influx. By contrast, -conotoxin GVIA (an inhibitor of N-type high-voltage-activated calcium channels), did not affect the DMDS-induced [Ca²⁺]_i rise. Finally, the participation of the calcium-induced calcium release mechanism was investigated using thapsigargin, caffeine, and ryanodine. Our study revealed that DMDS-induced elevation in [Ca²⁺]_i modulated IKCa in an unexpected bell-shaped manner via intracellular calcium. In conclusion, DMDS affects multiple targets, which could be an effective way to improve pest control efficacy of fumigation.

Address correspondence to: Dr. Bruno Lapied, Laboratoire Récepteurs et Canaux Ioniques Membranaires, Unité Propre de Recherche et de l'Enseignement Supérieur, Equipe d'Accueil 2647/USC Institut National de la Recherche Agronomique, Université d'Angers, Unité de Formation et de Recherche Sciences, 2 boulevard Lavoisier, F-49045 Angers cedex, France. E-mail: bruno.lapied{at}univ-angers.fr