Direct and indirect effects of an organophosphorus acetylcholinesterase inhibitor and of an oxime on a neuro-neuronal synapse

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Abstract
The action of an irreversible inhibitor of acetylcholinesterase (AChE), the organophosphorus compound, ecothiopate iodide, and of a reactivator of phosphorylated AChE, contrathion, were analysed on acetylcholine (ACh) receptors and cholinergic synaptic transmission in the buccal ganglion of Aplysia. At high concentration (above 10−4mol·l−1), both compounds exerted a curare-like depression on ACh receptors which was reversible with washing. Both compounds reversibly facilitated the current response to ionophoretic application of ACh and increased the evoked postsynaptic current (PSC) as well as the miniature postsynaptic currents (MPSCs). All responses also showed an increase in decay time. These modifications, when induced by ecothiopate iodide were irreversible by washing; however they could be reversed if first washed with contrathion. Neither the organophosphate compound or the oxime did change the number of quanta released per impulse. The current response to ionophoretic application of carbachol also increased after ecothiopate iodide was added. In the limits of the method used, the conductance and opening time of postsynaptic ionic channels opened by ACh were not found to be modified by the two compounds. It was concluded that the facilitatory action of the organophosphorus inhibitors cannot be solely explained by the inhibition of ACh hydrolysis.