Aging and 3,4-diaminopyridine alter synaptosomal calcium uptake.

The molecular basis of the cognitive changes that accompany aging is unknown. Since several lines of evidence suggest that senescence may alter calcium homeostasis, 45calcium uptake was determined in brain synaptosomes from aged rats. In low potassium (5 mM KCl) media, aging altered calcium influx: 104.2% (3 months), 100.0% (6 months), 76.7% (15 months), or 58.6% (27 months). In 31 mM KCl media, uptake declined with age from 106.6% (3 months) to 100.0% (6 months), 67.8% (15 months), or 45.8% (27 months). 3,4-Diaminopyridine elevated the potassium-stimulated calcium influx 2.3% (3 months), 10.2% (6 months), 31.8% (15 months), or 78.8% (27 months) when they are compared to non-drug-treated synaptosomes of the same age. The calcium that binds superficially to the plasma membrane changed as the age increased from 3 months (105.4%) to 6 months (100.0%), 15 months (116.1%), or 27 months (141.4%). 3,4-Diaminopyridine reduced this binding at 15 or 27 months to 109.3 or 121.4%, when compared to the 6 month old rats respectively. The decline in synaptosomal calcium uptake may alter neuronal metabolism which leads to the reduction in mental function that accompanies aging.