Cell-specific mRNA alterations in Na+, K+-ATPase α and β isoforms and FXYD in mice treated chronically with carbamazepine, an anti-bipolar drug

Neurochem Res. 2013 Apr;38(4):834-41. doi: 10.1007/s11064-013-0986-3. Epub 2013 Feb 10.


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 α subunits (α1-3) and two β subunits (β1 and β2) 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 α2 Expression was upregulated in astrocytes and neurons and α1 selectively in neurons, but α3 was unchanged. β1 was upregulated in astrocytes, but not in neurons. β2 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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / enzymology*
  • Bipolar Disorder / drug therapy
  • Carbamazepine / pharmacology*
  • Female
  • Isoenzymes / drug effects
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Mice
  • Nerve Tissue Proteins / biosynthesis*
  • Neurons / drug effects
  • Neurons / metabolism
  • RNA, Messenger / metabolism
  • Sodium-Potassium-Exchanging ATPase / drug effects
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Fxyd7 protein, mouse
  • Isoenzymes
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Carbamazepine
  • Atp1a1 protein, mouse
  • Sodium-Potassium-Exchanging ATPase