Uptake of 1-methyl-4-phenylpyridinium ion (MPP(+)) and ATP content in synaptosomes

Symptoms such as those in Parkinson's disease are known to be induced by the neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)). We tried to quantitatively measure synaptosomal MPP(+) uptake using an MPP(+) selective electrode to study the correlation between MPP(+) uptake and respiratory inhibition. Synaptosomal MPP(+) uptake was low but could be increased by the addition of glucose as an energy substrate, or increased with an increase in the concentration of MPP(+). The rate of uptake was 0.2umol/mg protein/min at 50 mu M MPP(+) Tetraphenylboron (TPB-), which enhances cation permeability, increased MPP(+) uptake, and the increase was proportional to the TPB- concentration. When external MPP(+) concentration was increased above 200 mu M, ATP was depleted and the uptake of MPP(+) decreased, which resulted in the release of intrasynaptosomal MPP(+). MPP (+) uptake was also decreased by depolarization of the membrane potential in synaptosomes. MPP(+) was presumed to be distributed across both the synaptosomal and inner mitochondrial membranes, and to be affected by membrane potential as a lipophilic cation. When respiration of the inner mitochondria was inhibited by increasing the intrasynaptosomal MPP(+) concentration, the concentration of MPP(+) in cytosol was presumed to increase by the release of MPP(+) from the mitochondria, and synaptosomal MPP(+) uptake would then be decreased.