Effect of post-hypoxic MgSO(4) administration in utero on Ca(2+)-influx and Ca(2+)/calmodulin kinase IV activity in cortical neuronal nuclei

Abstract

Previously we have demonstrated that in utero hypoxia results in increased nuclear Ca(2+)-influx and increased CaM kinase IV activity in neuronal nuclei of the guinea pig fetus. The present study tests the hypothesis that maternal treatment with magnesium sulfate (MgSO(4)) following in utero hypoxia will attenuate the hypoxia-induced increase in Ca(2+)-influx and CaM kinase IV activity in neuronal nuclei of the fetal guinea pig brain during recovery. Pregnant guinea pigs at 60 days of gestation were divided into four groups: normoxic (Nx=5), hypoxic (Hx, n=4), untreated post-hypoxic 24h recovery (Rec, n=8) and Mg(2+)-treated post-hypoxic 24h recovery (Mg(2+)-Rec, n=8). Maternal hypoxia was induced by decreasing FiO(2) to 8% for 1h. Recovery groups received either saline or 300 mg/kg MgSO(4) (i.p.) followed by 100mg/kg/h i.p. for 4h. Fetal cerebral tissue hypoxia was documented by ATP and phosphcreatine (PCr) levels. Neuronal nuclei were isolated and nuclear Ca(2+)-influx as well as CaM kinase activity was determined. Nuclear Ca(2+) influx (pmol/mg protein) was 4.84+/-0.83 in Nx, 12.50+/-2.97 (p<0.05) in Hx, 7.83+/-1.78 in Rec group (p<0.05 versus Nx and Hx) and 5.02+/-1.77 in Mg(2+)-Rec group (p<0.05 versus Rec group, p<0.05 versus Hx, p=NS versus Nx). CaM kinase IV activity (pmol/mg protein/min) was 1197+/-62 in Nx, 2524+/-132 (p<0.05 versus Nx) in Hx, 1830+/-141 (p<0.05 versus Nx and Hx) in Rec and 1938+/-118 in Mg(2+)-Rec group (p<0.05 versus Hx and Nx, p=n.s. versus Rec). The data show that MgSO(4) administration following in utero hypoxia prevents hypoxia-induced increase in neuronal nuclear Ca(2+)-influx but has no effect on CaM kinase activity in the guinea pig fetus during recovery. We conclude that post-hypoxic administration of Mg(2+) prevents hypoxia-induced modification of neuronal nuclear membrane function.