Competition between Li⁺ and Mg²⁺ in neuroblastoma SH-SY5Y cells: A fluorescence and ³¹P NMR study

Because Mg²⁺ and Li⁺ ions have similar chemical properties, we have hypothesized that Li⁺/Mg²⁺ competition for Mg²⁺ binding sites is the molecular basis for the therapeutic action of lithium in manic-depressive illness. By fluorescence spectroscopy with furaptra-loaded cells, the free intracellular Mg²⁺ concentration within the intact neuroblastoma cells was found to increase from 0.39 ± 0.04 mM to 0.60 ± 0.04 mM during a 40-min Li⁺ incubation in which the total intracellular Li⁺ concentration increased from 0 to 5.5 mM. Our fluorescence microscopy observations of Li⁺-free and Li⁺-loaded cells also indicate an increase in free Mg²⁺ concentration upon Li⁺ incubation. By ³¹P NMR, the free intracellular Mg²⁺ concentrations for Li⁺-free cells was 0.35 ± 0.03 mM and 0.80 ± 0.04 mM for Li⁺-loaded cells (final total intracellular Li⁺ concentration of 16 mM). If a Li⁺/Mg²⁺ competition mechanism is present in neuroblastoma cells, an increase in the total intracellular Li⁺ concentration is expected to result in an increase in the free intracellular Mg²⁺ concentration, because Li⁺ displaces Mg²⁺ from its binding sites within the nerve cell. The fluorescence spectroscopy, fluorescence microscopy, and ³¹P NMR spectroscopy studies presented here have shown this to be the case.