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

• Published in: Journal of neurophysiology Vol. 90; no. 1; pp. 259 - 270
• Main Authors: Dugravot, Sébastien, Grolleau, Françoise, Macherel, David, Rochetaing, Annie, Hue, Bernard, Stankiewicz, Maria, Huignard, Jacques, Lapied, Bruno
• Format: Journal Article
• Language: English
• Published: American Physiological Society 01-07-2003
• Subjects: Life Sciences; CHAINE RESPIRATOIRE; CANAL POTASSIUM; INSECTE
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01096.2002

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.