Abstract
The effects of HEOD and some of its metabolites on synaptic transmission in the frog motor end-plate were studied by means of intracellular microelectrodes. HEOD itself and the metabolites 9- syn-hydroxy-HEOD and the aldrin-derived dicarboxilic acid had no significant effect on frequency and amplitude of miniature end-plate potentials, nor on end-plate membrane potential. In sharp contrast with this aldrin-transdiol (6,7- trans-dihydroxy-dihydro-aldrin) was very potent in exerting both pre- and postsynaptic actions. This metabolite caused a rapid and marked increase in miniature end-plate potential frequency, together with a decrease in their amplitude. Evidence is presented suggesting that the spontaneous transmitter release is enhanced by two prejunctional mechanisms: partly by a calcium-dependent effect, probably a depolarization of the nerve terminal, and partly by a calcium-independent action. Another typical prejunctional action of aldrin-transdiol is the reduction of the amount of transmitter released in response to high external potassium concentration. Aldrin-transdiol also affected the evoked transmitter release and caused a marked increase in end-plate potential amplitude followed by a decrease, and finally a complete blockade of neuromuscular transmission was observed. This transient increase in transmitter release was shown to be due to a transient increase in quantal content. The subsequent fall in end-plate potential amplitude and the fall in miniature end-plate potential amplitude are probably the result of a reduction of the sensitivity of the postsynaptic membrane to acetylcholine as demonstrated by ionophoretic application of this transmitter. There was no aldrin-transdiol-effect on the end-plate membrane potential. The present results strongly support the hypothesis that HEOD must be converted to aldrin-transdiol before it can exert its neurotoxic action.
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