Analysis of Na+/Ca2+ exchange activity in human brain: the effect of normal aging

Na+/Ca2+ exchange activity and passive permeability to Ca2+ were analyzed in plasma membrane vesicles (PMV) purified from whole rat brain and three regions of human brain: frontal cortex, temporal cortex, and cerebellum. Accumulation of Ca2+ due to Na+/Ca2+ exchange activity showed a characteristic pattern of an initial rapid rise in Ca2+ content followed by a stable plateau in both rat and human brain. Total Ca2+ accumulation in rat brain PMV was on average three-fold higher than in human brain. Passive permeability to Ca2+ was measured as the rate of Ca2+ release from PMV first loaded with 45Ca by Na+/Ca2+ exchange and then exposed to 1 mM EGTA. The Ca2+ permeabilities of human and rat brain PMV were similar. Ca2+ release from rat brain PMV was faster overall and was resolved into fast and slow components while in human brain a single slow component was found. Post mortem delay up to 4 h had no effect on Na+/Ca2+ exchange Km for Ca2+, Vmax, and peak uptake and Ca2+ release rate in rat brain PMV. Human frontal cortex was shown to have a greater Na+/Ca2+ exchange activity than that found in the cerebellum. The frontal cortex, temporal cortex and cerebellum had similar Ca2+ permeabilities. Age-related effects on Na+/Ca2+ exchange activity and Ca2+ permeability were determined in 15 tissues from human frontal cortex (age at death 21 to 93 years). No significant age related effects were seen.(ABSTRACT TRUNCATED AT 250 WORDS)