DEVELOPMENTAL-CHANGES IN INTRACELLULAR CALCIUM REGULATION IN RAT CEREBRAL-CORTEX DURING HYPOXIA

During the first weeks of life, injury to the central nervous system c aused by brief periods of oxygen deprivation greatly increases. To inv estigate possible causes for this change, the effects of hypoxia or ap plication of the excitatory neurotransmitter glutamate on intracellula r calcium ([Ca2+]i) and ATP were studied in rat cerebrocortical brain slices. [Ca2+]i was measured fluorometrically with the indicator Fura- 2. Hypoxia (95% N2/5% CO2) or 100 muM sodium cyanide produced gradual elevations in [Ca2+]i and ATP depletion in slices from rats <2 weeks o ld, but rapid changes in older rats. After 20 min, [Ca2+]i in adult sl ices exposed to cyanide was 1,980 +/- 3 10 nM; in day 1-14 animals, it was 7% +/- 181 nM (p < 0.05). Combination of cyanide and a glycolytic inhibitor (iodoacetate) rapidly elevated [Ca2+]i and depleted ATP in all age groups. Energy utilization during anoxia, assessed by measurin g ATP fall in cyanide/iodoacetate-treated brain slices, increased with age. Elevations in [Ca2+]i caused by application of 500 muM glutamate increased 240% from days 1-2 to day 28, but ATP loss caused by glutam ate did not change with age. The N-methYl-D-aspartate antagonist MK-80 1 delayed calcium entry during the initial 5-7 min of hypoxia or cyani de in rats <2 weeks old. We conclude that anaerobic ATP production, co nservation of energy by reduced ATP consumption, and reduced sensitivi ty to glutamate contribute to delaying elevation in [Ca2+]i in neonata l rat brain during hypoxia.