ENERGY-METABOLISM OF ADULT ASTROCYTES IN-VITRO

In this study we established cultures of astrocytes from the forebrain of the adult rat. The homeostatic regulatory mechanisms of the aerobi c and anaerobic pathways of energy metabolism in these cells showed th at adult astrocytes express many of the regulatory properties previous ly demonstrated in neonatal astrocytes. Changes in mitochondrial respi ration and ATP production were readily evident upon incubation with th e relevant substrates. Inhibition of mitochondrial respiration led to a compensatory increase in anaerobic glycolysis as evidenced by an inc reased release of lactate. We assessed the role of cytosolic calcium i n the regulation of the mitochondrial energy metabolism. Increases in cytosolic calcium concentration in response to ATP or stimulation of m echanical receptors were followed by depolarizations of the mitochondr ial membrane potential, whose magnitude reflected the amplitude of the cytosolic calcium response. The changes in mitochondrial membrane pot ential were largely dependent on the presence of external calcium. The se results provide the first evidence of a signalling mechanism in ast rocytes by which changes in cytosolic calcium mediate changes in respi ration, possibly through mitochondrial calcium uptake and subsequent a ctivation of several mitochondrial dehydrogenases. This signalling pat hway would thus ensure that energy demands due to changes in cytosolic calcium concentrations are met by increases in energy production thro ugh increases in mitochondrial oxidative phosphorylation.