Involvement of mitochondria in the age-dependent decrease in calcium uptake of rat brain synaptosomes.

Calcium uptake in rat brain synaptosomes decreases during ageing. The possible involvement of mitochondria in altered calcium homeostasis has been investigated. Mitochondria isolated from old rat brain showed decreased calcium uptake rates. Since neither the mitochondrial membrane potential nor the delta pCa decreases with age, it was concluded that variations in the driving force for calcium uptake were not the cause for impaired calcium transport in mitochondria from aged rat brain. The steady state calcium distribution in isolated aged rat brain mitochondria was achieved at higher extramitochondrial calcium concentrations than that of adults. Studying the effects of the selective release of calcium from the mitochondrial pool by the addition of an uncoupler to 45Ca loaded synaptosomes incubated in high-potassium media, it was found that the intrasynaptic mitochondrial pool and the intra/extramitochondrial 45Ca distribution also decreased considerably in 24-month-old rats. Steady state fluorescence anisotropy (rs) of diphenylhexatriene-labelled mitoplasts from 'free' brain mitochondria increased with ageing. However, since no changes in rs from synaptosomal mitochondria were found in 24-month-old rats, it is suggested that alterations in lipid dynamics are not involved in the impaired calcium uptake observed in brain mitochondria from aged rats. The implications of these findings in the calcium homeostasis of brain endings are discussed.