Response of sodium pump to ouabain challenge in human glioblastoma cells in culture

Abstract

Bipolar disorder is a severe psychiatric condition that manifests with abnormalities in ion regulation. Previous studies have suggested that glia may be specifically involved in the pathophysiology of this condition. Since the potent sodium pump inhibitor, ouabain, has been used previously to model the ionic changes of bipolar illness, we investigated its effect of on sodium pump expression and activity in a human glioblastoma cell line. LN229 cells were grown with or without ouabain 10⁻⁷ M for 3 days, and the effect of a therapeutic concentration of lithium was also examined. The mRNA transcription of sodium pump isoforms was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and the protein expression of phosphorylated and non-phosphorylated pump isoforms was semi-quantified utilizing Western blot. Ouabain treatment caused an increase of some 6-fold in α1 protein expression and a doubling of α1 mRNA. α3 protein and α2 and α3 mRNA more than doubled. Lithium treatment alone had no effect, but lithium co-administered with ouabain normalized Na pump protein and mRNA expression for α1 and 2, but not α3. These results suggest that disturbance of ion regulation induces changes in glial cell sodium regulatory systems which are normalized by lithium treatment.

• Bipolar disorder
• glia
• lithium
• Na
• K-ATPase
• ouabain