Mechanisms, regulation and pathologic significance of Mg2+ efflux from erythrocytes.

Mg2+ efflux from erythrocytes can be performed by the Na+/Mg2+ antiport and by Na+-independent Mg2+ efflux. Na+-independent Mg2+ efflux functions via the unspecific choline exchanger as choline/Mg2+ or K+/Mg2+ antiport and as Mg2+ efflux accompanied by intracellular Cl- for charge compensation, as found for example in sucrose medium. Na+/Mg2+ antiport in erythrocytes exchanges 2 extracellular Na+ for 1 intracellular Mg2+. Driving forces are the Na+ and Mg2+ gradients. By reversing these gradients, the Na+/Mg2+ antiporter can mediate Mg2+ influx. The Na+/Mg2+ antiporter can exchange 24Mg2+ for 28Mg2+ and other divalent cations for intracellular Mg2+. In the exchange mechanism, extra- and intracellular Na+ can compete with Mg2+. Na+/Mg2+ antiport is inhibited by amiloride, quinidine and imipramine. Na+/Mg2+ antiport is drastically activated by intracellular Mg2+ due to an allosteric transition. The affinity of intracellular Mg2+ to the Na+/Mg2+ antiporter is dependent on intracellular ATP due to phosphorylation. Besides this mechanism, in non Mg2+-loaded erythrocytes, the activity of Na+/Mg2+ antiport is regulated by phosphorylation-dephosphorylation and by intracellular Cl-. The drastically Mg2+-activated Na+/Mg2+ antiporter is not further stimulated by phosphorylation and intracellular Cl-. Na+-independent Mg2+ efflux via the choline exchanger is also inhibited by amiloride, quinidine and imipramine, and can also be regulated by phosphorylation-dephosphorylation. Na+/Mg2+ antiport of erythrocytes is altered in various pathologic conditions.