Disruption of the potential across the synaptosomal plasma membrane and mitochondria by neurotoxic agents.

The effect of a neurotoxic organo-metal, methyl mercuric iodide, and an aromatic solvent, toluene, upon the transmembrane potential (psi), across both the limiting membrane of isolated nerve terminals and their mitochondria, has been studied. Exposure of nerve endings to either of these toxicants in vitro resulted in a dose-dependent diminution of psi that was especially pronounced in the case of mitochondria. This was not prevented by a concurrent exposure to an antioxidant (alpha-tocopherol), or an iron chelator (deferoxamine), or ganglioside GM1. No significant changes were detected in synaptosomal potentials derived from cortices of rats exposed to methyl mercury or toluene at levels known to increase the rate of formation of reactive oxygen species within this region. The special vulnerability of mitochondrial psi to these agents may be due to the disruption of oxidative phosphorylation and may be related to the increase in intrasynaptosomal free ionic calcium that both of these chemicals can induce.