Differential expression patterns of sodium potassium ATPase alpha and beta subunit isoforms in mouse brain during postnatal development.

The sodium potassium ATPase (Na+/K+ ATPase) is essential for the maintenance of a low intracellular Na+ and a high intracellular K+ concentration. Loss of function of the Na+/K+ ATPase due to mutations in Na+/K+ ATPase genes, anoxic conditions, depletion of ATP or inhibition of the Na+/K+ ATPase function using cardiac glycosides such as digitalis, causes a depolarization of the resting membrane potential. While in non-excitable cells, the uptake of glucose and amino acids is decreased if the function of the Na+/K+ ATPase is compromised, in excitable cells the symptoms range from local hyper-excitability to inactivating depolarization. Although several studies have demonstrated the differential expression of the various Na+/K+ ATPase alpha and beta isoforms in the brain tissue of rodents, their expression profile during development has yet to be thoroughly investigated. An immunohistochemical analysis of postnatal day 19 mouse brain showed ubiquitous expression of Na+/K+ ATPase isoforms α1, ß1 and ß2 in both neurons and glial cells, whereas α2 was expressed mostly in glial cells and the α3 and ß3 isoforms were expressed in neurons. Furthermore, we examined potential changes in the relative expression of the different Na+/K+ ATPase isoforms in different brain areas of postnatal day 6 and in adult 9 months old animals using immunoblot analysis. Our results show a significant up-regulation of the α1 isoform in cortex, hippocampus and cerebellum, whereas, the α2 isoform was significantly up-regulated in midbrain. The ß3 isoform showed a significant up-regulation in all brain areas investigated. The up-regulation of the α3 isoform matched that of the ß2 isoform which were both significantly up-regulated in cortex, hippocampus and midbrain, suggesting that the increased maturation of the neuronal network is accompanied by an increase in expression of α3/ß2 complexes in these brain structures.