Na+, K+-ATPase signaling and bipolar disorder

David Lichtstein*, Asher Ilani, Haim Rosen, Noa Horesh, Shiv Vardan Singh, Nahum Buzaglo, Anastasia Hodes

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations


Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the disease is poorly understood and its treatment is unsatisfactory. Although in past decades the “monoamine hypothesis” has dominated our understanding of both the pathophysiology of depressive disorders and the action of pharmacological treatments, recent studies focus on the involvement of additional neurotransmitters/neuromodulators systems and cellular processes in BD. Here, evidence for the participation of Na+, K+-ATPase and its endogenous regulators, the endogenous cardiac steroids (ECS), in the etiology of BD is reviewed. Proof for the involvement of brain Na+, K+-ATPase and ECS in behavior is summarized and it is hypothesized that ECS-Na+, K+-ATPase-induced activation of intracellular signaling participates in the mechanisms underlying BD. We propose that the activation of ERK, AKT, and NFκB, resulting from ECS-Na+, K+-ATPase interaction, modifies neuronal activity and neurotransmission which, in turn, participate in the regulation of behavior and BD. These observations suggest Na+, K+-ATPase-mediated signaling is a potential target for drug development for the treatment of BD.

Original languageAmerican English
Article number2314
JournalInternational Journal of Molecular Sciences
Issue number8
StatePublished - 7 Aug 2018

Bibliographical note

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.


  • AKT
  • Bipolar disorder
  • Cardiac steroids
  • Depression
  • ERK
  • K-ATPase
  • Mania
  • Na
  • Signaling


Dive into the research topics of 'Na+, K+-ATPase signaling and bipolar disorder'. Together they form a unique fingerprint.

Cite this