Ontogeny of Na⁺-K⁺-ATPase in the Brain of Fetal, Neonatal and Adult Sheep † 1098

The sodium pump, Na⁺-K⁺-ATPase, is a ubiquitious plasma membrane-bound class of enzymes responsible for Na⁺ and K⁺ translocation across cell membranes. Na⁺-K⁺-ATPase is essential for the generation of the electrochemical gradients that control the ionic environment necessary for neuronal activity. Therefore, this enzyme is likely to play a critical role in normal central nervous system development. As an initial attempt to examine the importance of this class of enzymes in ovine brain development, we examined the ontogeny of central nervous system Na⁺-K⁺-ATPase activity in the cortex of fetuses at 60% or 87 days (n=3), 80% or 120 days (n=6) of gestation, newborn lambs at 5 days of age(n=4) and adult ewes (n=4). Na⁺-K⁺-ATPase activity was estimated in crude total membrane preparations by the measurement of ouabain sensitive inorganic phosphate liberation from ATP expressed as mmoles P_i/mg protein/hr. Na⁺-K⁺-ATPase activity was 6.61 ± 1.16 (M± SD) at 60% of gestation, 12.56 ± 1.67 at 80% of gestation, 18.37 ± 1.44 in lambs, and 20.21 ± 2.22 in the adult (ANOVA, F=45.99, P<0.0001). The activity of Na⁺-K⁺-ATPase in the cortex increased three-fold from 60% percent of gestation through the postnatal period. An increase was not observed between the newborn and adult groups. Thus, the maximal activity observed was found by day 5 of life. We conclude that ontogenic increases in Na⁺-K⁺-ATPase activity are observed from early in fetal to neonatal life, but that after the neonatal period a further increase is not observed.