Effect of hypoxia on calcium influx and calcium/calmodulin-dependent kinase activity in cortical neuronal nuclei of the guinea pig fetus during development.

OBJECTIVE

Our purpose was to investigate the effect of hypoxia on calcium (Ca(++)) influx and Ca(++)-calmodulin (CaM)-dependent protein kinase IV (CaM kinase IV) activity in the neuronal nuclei of the guinea pig fetal cerebral cortex during development.

STUDY DESIGN

Preterm and term pregnant guinea pigs (n = 61) were exposed to either 21% or 7% oxygen for 60 minutes. Hypoxia in the fetal cerebral cortical tissue was documented by determining the tissue concentrations of adenosine triphosphate (ATP) and phosphocreatine. Fetal cerebral cortical neuronal nuclei were isolated and purified, and ATP-dependent Ca(++) influx and CaM kinase activity were determined.

RESULTS

Hypoxia resulted in increased neuronal intranuclear (45)Ca(++) influx for 2 minutes from 6.65 +/- 1.29 pmol/mg protein to 9.07 +/- 1.98 pmol/mg protein (P <.05) in preterm and from 6.65 +/- 1.63 pmol/mg protein to 11.26 +/- 1.79 pmol/mg protein (P <.05) in term fetuses. The hypoxia-induced (45)Ca(++) influx was significantly higher (P <.05) in the term than in the preterm fetuses. Hypoxia resulted in increased CaM kinase IV activity from 383.7 +/- 53.3 pmol/mg/min protein to 451.6 +/- 59.5 pmol/mg/min protein (P <.05) in the preterm and from 364.6 +/- 109.7 pmol/mg/min protein to 487.0 +/- 43.3 pmol/mg/min protein (P < 0.05) in term fetuses. No significant difference was observed in CaM kinase IV activity between the preterm and the term groups.

CONCLUSION

Cerebral hypoxia increases calcium influx and CaM kinase IV activity in the cortical neuronal nuclei of the guinea pig fetal brain during development.