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Insect Glutamatergic-Neuromuscular Synapse as a New Target of Organophosphate Compounds
Published online by Cambridge University Press: 19 September 2011
Abstract
The actions of diisopropylfluorophosphate (DFP), an irreversible anticholinestrase (Anti-ChE) agent, were studied on the glutamatergic neuromuscular synapse of insects. The present study reveals that DFP interacts with pre- and post-synaptic regions, also it gives alternative explanations of the symptoms of organophosphate poisoning in insects. Exposure of the metathoracic flexor tibialis muscle of Locusta migratoria to DFP (0.5 mM), at physiological solution, contained normal external calcium concentration (2 mM), increased spontaneous neurotransmitter release which was large enough to trigger action potentials (APs) and endplate potentials (EPPs). A cyclic pattern of APs and EPPs burses and silence periods were recorded. The spontaneous firing of APs and EPPs was calcium-dependent. Reduction of external calcium concentration abolished this phenomenon, suggesting a pre-synaptic site of action of DFP. A transient pre-synaptic depolarization, caused by the agent, could explain the spontaneous transmitter release and repetitive EPPs firing. The spontaneous activity, induced by DFP, was blocked by a sodium channel blocker such as tetrodotoxin. Exposure to α-bungarotoxin, α-Naja-toxin or atropine did not affect the spontaneous release of the transmitter induced by OP agent. Coupled with the pre-synaptic effect, a decrease in the peak amplitude of endplate current (EPC) and shortening of the decay time constant (τEPC) recorded after exposure to the flexor muscle to 1 mM DFP. Both the pre- and post-synaptic effects of DFP were reversible upon washing the preparation. The present findings shift the focus of the occasioners of hyperexcitation of insects treated with OPs from indirect effects of these compounds on the central nervous system (CNS) to direct effects on neuromuscular junctions and indirect effects on CNS.
Résumé
Les actions du diisopropylfluorophosphate (DFP), un agent anti-cholinergique (anti-ChE) irreversible, ont été étudié sur les synapses neuromusculaires glutamatergiques des insectes. La présente étude révèle que le DFP intervient avéc les régions pré-et postsynaptiques, il donne aussi des explications alternatives sur les symptomes d'empoisonnement par organophosphates chez les insectes. L'exposition du muscle metathoracique flexeur du tibia de Locusta migratoria à une concentration de (0.5 mM) de DFP, en utilisant une solution physiologique contenant une concentration externe normale de calcium (2 mM), a augmente l'émission spontanée de neurotransmetteur suffisament importante pour déclencher des actions de potentiels (APs) ainsi que des potentiels de terminaison du nerf (EPPs). Un modèle cyclique de (APs), de (EPPs) et de périodes de silence fut enregistré. Cette émission spontanée des potentiels (APs) et (EPPs) était dépendente du calcium. La réduction de la concentration externe de calcium a aboli ce phénomène, suggérant un site présynaptique d'action de DFP. Une dépolarization présynaptique transitoire, causée par l'agent, pourait expliquer l'émission spontanée du transmetteur ainsi que la décharqe répéttée de (EPPs). L'activité spontanée provoquée par DFP fut bloquée par un bloceur du canal de sodium comme le tetrodotoxin. L'exposition des préparations aux toxines telles que α-bungarotoxin, α-Najatoxin ainsi que l'atropine montre que ces substances n'eurent aucun effet sur l'émission spontanée du transmetteur provoquée par l'agent OP. Associé ā l'effet présynaptique, il fut enregistré une diminution du pic d'amplitude du courent (EPC), ainsi qu'une diminution de la constante du temps de déclin du courent (τEPC) et ceci après l'exposition du muscle flexeur ā une concentration de 1 mM DFP. La présente étude déplace le foyer de l'intérêt concentré, sur les effets indirects des composés OPs sur le système nerveux central (CNS), aux effets directs sur les jonctions neuromusculaires, ainsi qu'aux effets indirects sur le CNS.
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