Effects of Li+ transport and Li+ immobilization on Li+/Mg2+ competition in cells: Implications for bipolar disorder

Brian T. Layden, Abde M. Abukhdeir, Nicole Williams, Carla P. Fonseca, Laura Carroll, Margarita M C A Castro, Carlos F G C Geraldes, Fred B. Bryant, Duarte Mota De Freitas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Li+/Mg2+ competition has been implicated in the therapeutic action of Li+ treatment in bipolar illness. We hypothesized that this competition depended on cell-specific properties. To test this hypothesis, we determined the degree of Li+ transport, immobilization, and Li+/Mg2+ competition in lymphoblastomas, neuroblastomas, and erythrocytes. During a 50mmol/L Li +-loading incubation, Li+ accumulation at 30min (mmoles Li+/L cells) was the greatest in lymphoblastomas (11.1±0.3), followed by neuroblastomas (9.3±0.5), and then erythrocytes (4.0±0.5). Li+ binding affinities to the plasma membrane in all three cell types were of the same order of magnitude; however, Li + immobilization in intact cells was greatest in neuroblastomas and least in erythrocytes. When cells were loaded for 30min in a 50mmol/L Li +-containing medium, the percentage increase in free intracellular [Mg2+] in neuroblastoma and lymphoblastoma cells (∼55 and ∼52%, respectively) was similar, but erythrocytes did not exhibit any substantial increase (∼6%). With the intracellular [Li+] at 15mmol/L, the free intracellular [Mg2+] increased by the greatest amount in neuroblastomas (∼158%), followed by lymphoblastomas (∼75%), and then erythrocytes (∼50%). We conclude that Li+ immobilization and transport are related to free intracellular [Mg 2+] and to the extent of Li+/Mg2+ competition in a cell-specific manner.

Original languageEnglish (US)
Pages (from-to)1915-1924
Number of pages10
JournalBiochemical Pharmacology
Volume66
Issue number10
DOIs
StatePublished - Nov 15 2003

Keywords

  • Atomic absorption
  • Fluorescence
  • Lymphoblastoma
  • NMR
  • Neuroblastoma

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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