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

Abstract

The present study was designed 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 Ca(2+)-influx was determined using (45)Ca(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 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 Ca(2+)-influx during hypoxia in newborn piglets 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 Ca(2+) is due to altered nuclear membrane Ca(2+)-influx mechanisms and will lead to Ca(2+)-mediated alteration of apoptotic gene expression as well as Ca(2+)-dependent activation of endonucleases that result in DNA fragmentation and subsequent programmed neuronal cell death.