Cell-Specific mRNA Alterations in Na+, K+-ATPase α and β Isoforms and FXYD in Mice Treated Chronically with Carbamazepine, an Anti-Bipolar Drug

Evidence accumulating during almost 50 years suggests Na+, K+-ATPase dysfunction in bipolar disorder, a disease treatable with chronic administration of lithium salts, carbamazepine or valproic acid. Three Na+, K+-ATPase alpha subunits (alpha 1-3) and two beta subunits (beta 1 and beta 2) are expressed in brain together with the auxiliary protein FXYD7. FXYD7 decreases K+ affinity, and thus contributes to stimulation of the enzyme at elevated extracellular K+ concentrations. Na+, K+-ATPase subtype and FXYD7 genes were determined by RT-PCR in mice co-expressing one fluorescent signal with an astrocytic marker or a different fluorescent signal with a neuronal marker and treated for 14 days with carbamazepine. Following fluorescence-activated cell sorting of neurons and astrocytes it was shown that alpha 2 Expression was upregulated in astrocytes and neurons and alpha 1 selectively in neurons, but alpha 3 was unchanged. beta 1 was upregulated in astrocytes, but not in neurons. beta 2 was unaffected in astrocytes and absent in neurons. FXYD7 was downregulated specifically in neurons. According to cited literature data these changes should facilitate K+ uptake in neurons, without compromising preferential uptake in astrocytes at increased extracellular K+ concentrations. This process seems to be important for K+ homeostasis of the cellular level of the brain (Xu et al. Neurochem Res E-pub Dec. 12, 2012).