Effects of magnesium sulfate administration during hypoxia on Ca2+ influx and IP3 receptor modification in cerebral cortical neuronal nuclei of newborn piglets

Magnesium is a non-competitive antagonist of the NMDA receptor. Hypoxic insults to the brain are associated with a significant increase in the intranuclear Ca2+ due to altered nuclear membrane Ca2+ in flux mechanisms including hypoxia-induced modi. cations of nuclear membrane IP3 receptors. In this study we have examined the effects of magnesium sulfate administration to newborn piglets subjected to normoxia and severe hypoxia. The animals were randomly divided into normoxic ( n = 4), hypoxic ( n = 4) and magnesium sulfate treated hypoxic ( n = 4) groups. Hypoxia was confirmed biochemically by measuring ATP and phosphocreatine ( PCr) levels in the brain tissue. Intranuclear Ca2+ in flux was assessed by measuring Ca-45(2+) uptake. Results show a significant ( P < 0.05) decrease in ATP and PCr levels in hypoxic group in comparison with normoxia. On the other hand magnesium-treated hypoxic group showed a significantly ( P < 0.05) higher ATP and PCr in comparison with the hypoxic group. Intranuclear Ca2+ was significantly ( P < 0.05) higher in the hypoxic group in comparison with both normoxic and magnesium-treated hypoxic groups. In addition results show that magnesium prevented hypoxia-induced modi. cation of the IP3 receptor. Magnesium treatment significantly reduced the hypoxia-induced increase in the number of receptors ( reduced B-max - P < 0.05 - treated hypoxia vs. hypoxia and normoxia), and reversed the receptor affinity ( reduced dissociation coefficient-K-d-P < 0.05 - treated hypoxia vs. normoxia). The results demonstrate that the administration of magnesium sulfate prior to hypoxia prevents the hypoxia-induced increase in intranuclear Ca2+ and IP3 receptor modi. cations. We conclude that Mg2+ administration prevents hypoxia-induced modi. cation of neuronal nuclear membrane function that leads to intranuclear Ca2+-dependent transcription of apoptotic proteins leading to hypoxic neuronal programmed cell death.