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

Abstract Age-related changes in resting levels of the free intracellular calcium concentration ([Ca 2+ ] i ) as well as alterations of the rise in [Ca 2+ ] i following depolarization have been investigated in acutely isolated cells of the mouse brain and of various regions of the rat brain. Resting [Ca 2+ ] i as well as Ca 2+ 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 Ca 2+ homeostasis is specially susceptible to the aging process in some brain regions only, resulting in a down regulation of [Ca 2+ ] i probably as a consequence of an enhanced sensitivity of mechanisms regulating [Ca 2+ ] 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 Ca 2+ homeostasis in the mouse and the rat were paralleled by comparable changes of [Ca 2+ ] i in spleenocytes of both species in aging. The rise of [Ca 2+ ] i after stimulation with the mitogen phytohemagglutinin (PHA) was significantly reduced in the plateau phase, which is maintained by Ca 2+ influx mechanisms. Moreover, a reduced Ca 2+ response was also found after stimulation of the cells with the Ca 2+ ionophore A23187. The data may indicate that comparable disturbances of the Ca 2+ homeostasis occur in central and peripheral cells and that these alterations mainly affect transmembraneous Ca 2+ fluxes rather than Ca 2+ 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 Ca 2+ homeostasis may result in a reduced capacity for adaptation. This assumption was supported by observations indicating that the down-regulation of [Ca 2+ ] i after subchronic treatment with nimodipine (20 mg kg , 14 days) was less in brain cells of aged than of young mice.