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

Abstract Li + /Mg 2+ 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 + /Mg 2+ competition in lymphoblastomas, neuroblastomas, and erythrocytes. During a 50 mmol/L Li + -loading incubation, Li + accumulation at 30 min (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 30 min in a 50 mmol/L Li + -containing medium, the percentage increase in free intracellular [Mg 2+ ] 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 15 mmol/L, the free intracellular [Mg 2+ ] 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 + /Mg 2+ competition in a cell-specific manner.