Hypoxia-induced Ca2+-influx in cerebral cortical neuronal nuclei of newborn piglets

The present study was desioned to investigate the effect of hypoxia on nuclear calcium-influx in the cerebral cortex of newborn piglets. Anesthetized and ventilated newborn piglets divided into normoxic (n = 4) and hypoxic groups with varying degrees of tissue hypoxia (n = 10) were studied. Nuclear Ca2+-influx was determined using Ca-45(2+) and plotted against ATP and phosphocreatine levels. The plots were analyzed by non-linear regression (exponential) analysis that showed a curvilinear relationship (r = 0.92 for ATP and r = 0.88 for P phosphocreatine). These data suggest a threshold at which there is a sudden increase in the nuclear calcium-influx that then continues to increase with further decrease in the ATP and phosphocreatine levels. The results demonstrate an increase in the nuclear Ca2+ -influx during hypoxia in newborn pialets and that this increase correlates in a curvilinear fashion with the increase in the degree of cerebral tissue hypoxia. We propose that the hypoxia-induced increase in intranuclear Ca2+ is due to altered nuclear membrane Ca2+-influx mechanisms and will lead to Ca2+-mediated alteration of apoptotic gene expression as well as Ca2+ -dependent activation of endonucleases that result in DNA fragmentation and subsequent programmed neuronal cell death. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.