Neuronal interaction determines the expression of the alpha-2 isoform of Na, K-ATPase in oligodendrocytes

Na,K-ATPase is an integral membrane enzyme responsible for maintenance of t he transmembrane Na+/K+ gradient which generates membrane excitability. Pre vious studies showed that oligodendrocytes within the CNS robustly expresse d the alpha2 isoform of the Na,K-ATPase while oligodendrocytes in isolated cultures did not. We tested whether the levels of this isoform might be mod ulated by interactions with neurons. Western blots showed alpha2 protein ex pression was very low in rat optic nerve immediately after birth, but that expression was greatly increased by days 5 and 14. In adult optic nerves, l evels were barely detectable. Since the first myelinated axons are observed in rat optic nerve at day 5, and the next 2 weeks are considered the perio d of peak myelination, this timing suggested a relationship between oligode ndrocyte-neuron contact, myelination onset and the upregulation of the alph a2 isoform. In further experiments we plated oligodendrocytes in isolation or in co-culture with neurons dissociated from cerebral cortex at the day o f birth. After 6 days in vitro, 45% of oligodendrocytes co-cultured with ne urons expressed abundant alpha2 protein which was detected by immunohistoch emistry, a six-fold increase over cells expressing alpha2 protein in isolat ed cultures. Conditioned medium from neuronal cultures did not affect alpha 2 levels in oligodendrocytes. These results suggest that neurons may play a role in upregulating glial expression of the alpha2 isoform during peak pe riods of myelination, and that the effect is: likely to be dependent on con tact. (C) 2000 Elsevier Science B.V. All rights reserved.