CYTOSOLIC AND MITOCHONDRIAL CALCIUM IN SYNAPTOSOMES DURING AGING

Synaptosomal [Ca2+](i) levels increase during aging, particularly in t he old rat hippocampus, both under basal conditions and after high K d epolarization. This is probably the result of age-dependent modificati ons in calcium buffering and extrusion systems rather than due to incr eased calcium influx, since calcium uptake through synaptosomal voltag e gated calcium channels decreases in old animals. The calcium binding capacity of the cytosolic compartment (i.e, that excluded from mitoch ondria and endoplasmic reticulum) of synaptosomes was markedly reduced in old rats. Calcium compartmentation in synaptosomal mitochondria, i s also reduced during aging, and this is associated with a decrease in activity of the mitochondrial calcium uniporter. Taken together, thes e modifications point towards a clear deterioration of the cell calciu m homeostatic mechanisms towards increased [Ca2+](i) in old age, speci ally under conditions of high calcium loads, a situation that may exac erbate neuronal vulnerability to excitotoxicity.