Down-regulation of free intracellular calcium in dissociated brain cells of aged mice and rats.

Age-related changes in resting levels of the free intracellular calcium concentration ([Ca2+]i) as well as alterations of the rise in [Ca2+]i following depolarization have been investigated in acutely isolated cells of the mouse brain and of various regions of the rat brain. Resting [Ca2+]i as well as Ca2+ responses after depolarization were lower in brain cells of aged mice and in hippocampus and cortex cells, but not striatum or cerebellum cells of aged rats. It is concluded that the Ca2+ homeostasis is specially susceptible to the aging process in some brain regions only, resulting in a down regulation of [Ca2+]i probably as a consequence of an enhanced sensitivity of mechanisms regulating [Ca2+]i. This speculation was confirmed by an enhanced sensitivity of Ca(2+)-stimulated phospholipase C activity in the aging mouse brain. The alterations of the central Ca2+ homeostasis in the mouse and the rat were paralleled by comparable changes of [Ca2+]i in spleenocytes of both species in aging. The rise of [Ca2+]i after stimulation with the mitogen phytohemagglutinin (PHA) was significantly reduced in the plateau phase, which is maintained by Ca2+ influx mechanisms. Moreover, a reduced Ca2+ response was also found after stimulation of the cells with the Ca2+ ionophore A23187. The data may indicate that comparable disturbances of the Ca2+ homeostasis occur in central and peripheral cells and that these alterations mainly affect transmembraneous Ca2+ fluxes rather than Ca2+ release from intracellular stores. These alterations may be compensated under normal conditions. However, in situations of additional stress like ischemia or hypoglycemia, the preexisting alterations of Ca2+ homeostasis may result in a reduced capacity for adaptation. This assumption was supported by observations indicating that the down-regulation of [Ca2+]i after subchronic treatment with nimodipine (20 mg/kg, 14 days) was less in brain cells of aged than of young mice.