Effect of chronic Li+ treatment on free intracellular Mg2+ in human neuroblastoma SH-SY5Y cells

Objective: Previous findings have demonstrated Li+/Mg2+ competition at therapeutic intracellular Li+ levels after acute Li+ treatment in human neuroblastoma SH-SY5Y cells. In the current study, we examined whether Li+/Mg2+ competition exists at therapeutically relevant extra- and intracellular [Li+] after chronic Li+ loading times. Methods: In human neuroblastoma cells, intracellular free Mg2+ was determined by fluorescence spectroscopy with the fluorophore furaptra. Intracellular Li+ and Mg2+ were measured by atomic absorption spectrophotometry. Results: After loading of the neuroblastoma cells with 1-2 mM extracellular Li+ for 24-72 h, the observed, increased intracellular free [Mg2+] levels were significantly higher (p < 0.03) than those in matched Li+ free cells, and intracellular [Li+] was found to be at therapeutic intracellular levels (0.7-1.5 mM). Conclusions: The results demonstrate that Li+/Mg2+ competition exists after chronic treatment with Li+ at therapeutically relevant intracellular Li+ levels in neuroblastoma cells. We found differences between acute and chronic Li+ treatment effects on the extent of Li+ /Mg2+ competition. Possible reasons for these differences are discussed.