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

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.