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Dimethyl Disulfide Exerts Insecticidal Neurotoxicity Through Mitochondrial Dysfunction and Activation of Insect K_ATP Channels

¹Institut de Recherche sur la Biologie de l'Insecte, UMR Centre National de la Recherche Scientifique 6035, Université de Tours, F-37200 Tours; ²Laboratoire de Neurophysiologie, Unité Propre de Recherche de l'Enseignement Supérieur Equipe d'Accueil 2647, Université d'Angers, Unité de Formation et de Recherche Sciences, F-49045 Angers Cedex 01; ³Unité Mixte de Recherche Physiologie Moléculaire des Semences, F-49045 Angers Cedex 01; ⁴Laboratoire de Préconditionnement et remodelage du myocarde, Université d'Angers, Unité de Formation et de Recherche Sciences médicales, F-49045 Angers Cedex 01, France; and ⁵Laboratory of Biophysics, N. Copernicus University, 87–100 Torun, Poland

Submitted 6 December 2002; accepted in final form 2 February 2003

The plant-derived insecticides have introduced a new concept in insecticide research. In response to insect attacks, some plants can release volatile sulfur compounds such as dimethyl disulfide (DMDS) in the atmosphere, which are lethal for the generalist insects. We demonstrate that DMDS induced an uncommon complex neurotoxic activity. The studies of in vivo toxicity of DMDS in three insect species and mice indicated a highest bioactivity for insects. Although DMDS did not alter the electrophysiological properties of the cockroach Periplaneta americana giant axon, it affected the synaptic transmission at the presynaptic level resulting in an inhibition of the neurotransmitter release. Whole cell patch-clamp experiments performed on cockroach cultured dorsal unpaired median (DUM) neurons revealed a dose-dependent hyperpolarization induced by DMDS associated with a decrease in the input resistance and the disappearance of action potentials. The hyperpolarization was inhibited by glibenclamide and tolbutamide, and was dependent on intracellular ATP concentration, demonstrating a neurotoxicity via the activation of K_ATP channels. Finally, the same effects observed with oligomycin, 2,4-dinitrophenol, and KCN together with the studies of DMDS toxicity on isolated mitochondria confirmed an unusual action occurring through an inhibition of the mitochondrial respiratory chain complex IV (cytochrome oxydase). This DMDS-induced inhibition of complex IV subsequently decreased the intracellular ATP concentration, which thereby activated neuronal K_ATP channels mediating membrane hyperpolarization and reduction of neuronal activity.

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