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.