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Lithium normalizes elevated intracellular sodium


  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Rif S El-Mallakh, MD, Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY 40292, USA. Fax: +1 502 852 1115; e-mail:


Background:  Both mania and bipolar depression are characterized by elevations of intracellular sodium concentrations. This observation has been purported to be central to the pathophysiology of abnormal moods in bipolar illness. Reduction of sodium influx is a proposed shared mechanism of action of effective mood stabilizers, but direct documentation of this effect for lithium has never been demonstrated.

Methods:  Flame spectroscopic determinations of intracellular sodium concentration were performed in the human glioma cell line, LN292, after treatment with the sodium pump inhibitor, ouabain, and co-treatment with ouabain and lithium.

Results:  Ouabain 0.1 μM doubles the intracellular sodium concentration after 3 days. Pretreatment with lithium 1 mM for 1 week normalizes intracellular sodium.

Conclusion:  This is the first demonstration that lithium can normalize abnormally elevated intracellular sodium levels. This may be an important mechanism of lithium action.