Na+, k+-atpase α isoforms and endogenous cardiac steroids in prefrontal cortex of bipolar patients and controls

Shiv Vardan Singh, Olga V. Fedorova, Wen Wei, Haim Rosen, Noa Horesh, Asher Ilani, David Lichtstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Bipolar disorder is a chronic multifactorial psychiatric illness that affects the mood, cognition, and functioning of about 1–2% of the world’s population. Its biological basis is unknown, and its treatment is unsatisfactory. The α1, α2, and α3 isoforms of the Na+, K+-ATPase, an essential membrane transporter, are vital for neuronal and glial function. The enzyme and its regulators, endogenous cardiac steroids like ouabain and marinobufagenin, are implicated in neuropsychiatric disorders, bipolar disorder in particular. Here, we address the hypothesis that the α isoforms of the Na+, K+-ATPase and its regulators are altered in the prefrontal cortex of bipolar disease patients. The α isoforms were determined by Western blot and ouabain and marinobufagenin by specific and sensitive immunoassays. We found that the α2 and α3 isoforms were significantly higher and marinobufagenin levels were significantly lower in the prefrontal cortex of the bipolar disease patients compared with those in the control. A positive correlation was found between the levels of the three α isoforms in all samples and between the α1 isoform and ouabain levels in the controls. These results are in accordance with the notion that the Na+, K+-ATPase-endogenous cardiac steroids system is involved in bipolar disease and suggest that it may be used as a target for drug development.

Original languageAmerican English
Article number5912
Pages (from-to)1-16
Number of pages16
JournalInternational Journal of Molecular Sciences
Issue number16
StatePublished - 2 Aug 2020

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  • Bipolar disorder
  • Endogenous cardiac steroids
  • Human
  • Marinobufagenin
  • Na, K-ATPase
  • Ouabain
  • Postmortem
  • Prefrontal cortex
  • α isoforms


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