Mechanisms and regulation of Mg2+ efflux and Mg2+ influx.

Net Mg2+ efflux occurred in human, chicken and rat erythrocytes, rat thymocytes and HL60 cells when the concentration of intracellular free Mg2+ ([Mg2+]i) was experimentally increased and proceeded until the original cellular Mg2+ content was reached, indicating induction and regulation of net Mg2+ efflux by increased [Mg2+]i. Net Mg2+ efflux was performed by electroneutral Na+/Mg2+ antiport, driven by the extra-/intracellular Na+ gradient. Na+/Mg2+ antiport was irreversible, performing only net Mg2+ efflux. Na+/Mg2+ antiport was inhibited by amiloride, quinidine and imipramine. Besides increased [Mg2+]i, Na+/Mg2+ antiport in thymocytes was regulated by cAMP which induced a maximal rate of Na+/Mg2+ antiport. Net Mg2+ influx occurred when the cellular Mg2+ content was experimentally reduced and stopped when after reincubation in suitable media the original cellular Mg2+ content was reached, indicating regulation by [Mg2+]i via feedback inhibition. Net Mg2+ influx in isolated hepatocytes was dependent on extracellular Mg2+, Na+, Cl-, HCO3- and Pi. Net Mg2+ influx may operate via electroneutral Na+, Mg2+/anion cotransport, driven by the extra-/intracellular Na+ gradient. However, electrogenic Mg2+ influx gated by extracellular Na+ and anions cannot be excluded. Net Mg2+ influx was stimulated by cAMP and inhibited by amiloride and verapamil. Net Mg2+ efflux and net Mg2+ influx are separate and regulated pathways, establishing homeostasis of intracellular Mg2+.