REGION-SPECIFIC DOWN-REGULATION OF FREE INTRACELLULAR CALCIUM IN THE AGED RAT-BRAIN

Age-related changes in resting levels of the free intracellular calciu m concentration ([Ca2+](i)) as well as alterations of the rise in [Ca2 +](i) following depolarization have been investigated in acutely isola ted brain cells of various regions of the rat brain. Characterization of the Ca2+ responses following KCl depolarization in the hippocampus, cortex, striatum, and cerebellum of young rats revealed significant r egional differences in the basal [Ca2+](i) level as well as in the KCl -induced rise in [Ca2+](i). However, there was no correlation between both parameters. Resting [Ca2+](i) as well as Ca2+ responses after dep olarization were lower in the hippocampus and cortex of the aged anima ls, but not in the striatum or cerebellum. It is concluded that the Ca 2+ homeostasis in the first two regions is specially susceptible to th e aging process, resulting in a downregulation of [Ca2+](i), probably as a consequence of an enhanced sensitivity of mechanisms regulating t ransmembraneous Ca2+ fluxes. The cellular Ca2+ homeostasis was altered in a comparable way in rat spleenocytes. The rise in [Ca2+](i) in the aged animals following stimulation of lymphocytes with the mitogen ph ytohemagglutinin (PHA) was significantly reduced in the plateau phase, which is maintained by Ca2+ influx mechanisms. The data indicate that age related disturbances of the cellular Ca2+ homeostasis may be pres ent in different cell types and seem to affect mainly transmembraneous Ca2+ flux much more than intracellular Ca2+ release.