Differential effects of age on the pathways of calcium influx into nerve terminals.

Calcium accumulation by synaptosomes decreases during ageing and this is partly due to an impaired calcium uptake by mitochondria (Brain Research, 378 (1986) 36-48). In the present work we have sought to define that effect of age on the pathways of K+-stimulated calcium influx. The plasma membrane potential of synaptosomes incubated at different K+ concentrations in choline-based or sodium-based media monitored with TPP+ did not change significantly with age. 45Ca uptake was reduced by around 20% in 24-vs 3-month-old rats at high K+ concentrations in both choline- and sodium-based media. However, the internal free calcium concentration in K+-depolarized synaptosomes estimated by the quin-2 method was found to be higher in 24- than in 3-month-old rats. When the apparent calcium permeabilities (P'Ca) in choline-based media were calculated from the corresponding calcium uptake values, membrane potentials and internal calcium concentration, it was found that the P'Ca values from old rats were only slightly lower than those of adults over the whole range of membrane potentials. The contribution of the Na/Ca exchanger to 45Ca uptake was estimated at different voltages by subtracting the normalized calcium uptake values obtained in choline media from those in Na media. The 'estimated' Na/Ca exchange was found to decrease markedly with age. Our results suggest that under our experimental conditions the apparent calcium permeability of synaptosomes is only modestly decreased during ageing. However, the operation of 45Ca/Na exchange is markedly reduced maybe as a result of alterations of the exchanger itself or due to changes in the concentration of internal Na or other ions.