Li+/Mg2+ competition at therapeutic intracellular Li+ levels in human neuroblastoma SH-SY5Y cells.

Abstract

OBJECTIVES:

One proposed mechanism of lithium action in the treatment of bipolar disorder is that Li+ competes with Mg2+ for Mg2+ binding sites within the cell. In this study, we investigated this competition at therapeutic intracellular Li+ levels in human neuroblastoma SH-SY5Y cells.

METHODS:

We used fluorescence spectroscopy and a Mg2+ indicator, furaptra, to investigate this competition in human neuroblastoma SH-SY5Y cells. Atomic absorption spectrophotometry was used for determination of the intracellular Li+ levels.

RESULTS:

The neuroblastoma cells, incubated in 15 mM or 30 mM Li+-containing buffer, showed a significant increase in free intracellular Mg2+ levels [using a positive linear within-groups contrast t-test, the 15 mM condition produced t(2) = 5.0, one-tailed p < 0.02, and the 30 mM Li+-incubation conditions gave t(2) = 9.2, one-tailed p < 0.006] but did not significantly increase over time in the Li+-free condition [t(2) = 0.1, one-tailed p > 0.96]. At the earlier times during the incubation (1 or 10 min for the 15 mM or 30 mM Li+-containing buffers), the intracellular Li+ concentrations were 0.6-2.5 mM, values which are comparable to those reached in the brain of Li+-treated patients.

CONCLUSION:

We demonstrated that competition between Li+ and Mg2+ can occur at therapeutic intracellular Li+ levels.

• Authors: B Layden, C Diven, N Minadeo, F B Bryant, D Mota de Freitas
• Journal: Bipolar disorders (Bipolar Disord) Vol. 2 Issue 3 Pt 1 Pg. 200-4 (Sep 2000) ISSN: 1398-5647 [Print] Denmark
• PMID: 11256688 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ion Channels
• Lithium
• Magnesium

Topics

• Bipolar Disorder (drug therapy, metabolism)
• Humans
• Intracellular Fluid (metabolism)
• Ion Channels (drug effects, metabolism)
• Ion Transport (drug effects)
• Lithium (metabolism, pharmacology)
• Magnesium (metabolism)
• Neuroblastoma (metabolism)
• Spectrophotometry, Atomic
• Tumor Cells, Cultured