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


CONCLUSIONS
We demonstrated that competition between Li+ and Mg2+ can occur at therapeutic intracellular Li+ levels.
Department of Chemistry, Loyola University Chicago, IL 60660, USA.
B
B
Layden
C
C
Diven
N
N
Minadeo
F B
FB
Bryant
D
D
Mota de Freitas
D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D008094:Lithium / Q000378:metabolism* / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D014407:Tumor Cells, Cultured
D007473:Ion Channels; D008094:Lithium; D008274:Magnesium