Developmental changes in intracellular calcium regulation in rat cerebral cortex during hypoxia.
During the first weeks of life, injury to the central nervous system caused by brief periods of oxygen deprivation greatly increases. To investigate possible causes for this change, the effects of hypoxia or application of the excitatory neurotransmitter glutamate on intracellular 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 microM sodium cyanide produced gradual elevations in [Ca2+]i and ATP depletion in slices from rats < 2 weeks old, but rapid changes in older rats. After 20 min, [Ca2+]i in adult slices exposed to cyanide was 1,980 +/- 310 nM; in day 1-14 animals, it was 796 +/- 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 measuring ATP fall in cyanide/iodoacetate-treated brain slices, increased with age. Elevations in [Ca2+]i caused by application of 500 microM glutamate increased 240% from days 1-2 to day 28, but ATP loss caused by glutamate did not change with age. The N-methyl-D-aspartate antagonist MK-801 delayed calcium entry during the initial 5-7 min of hypoxia or cyanide in rats < 2 weeks old. We conclude that anaerobic ATP production, conservation of energy by reduced ATP consumption, and reduced sensitivity to glutamate contribute to delaying elevation in [Ca2+]i in neonatal rat brain during hypoxia.
Bickler
P E
PE
Department of Anesthesia, University of California, San Francisco.
Gallego
S M
SM
Hansen
B M
BM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003486:Cyanides / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley
D003486:Cyanides; D005971:Glutamates; D007461:Iodoacetates; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium; D019807:Iodoacetic Acid