Putative mechanism of Mg2+/Mg2+ exchange and Na+/Mg2+ antiport

A putative mechanism of Mg2+/Mg2+ exchange and Na+/Mg2+ antiport is presented. The membrane-spanning Mg2+ transport protein may contain a selectivity filter, consisting of negatively charged amino acid residues in a ring-like structure as is the case in other transport proteins. Mg2+ is bound to the selectivity filler and blocks permeation of Mg2+ and other cations through the channel in Mg2+-unloaded cells. This bound Mg2+ can only be exchanged for radioactive Mg2+, yielding Mg2+/Mg2+ exchange without net Mg2+ transport. It can operate from both sides of the cell membrane. In Mg2+-loaded erythrocytes, 2 Mg2+ may be bound to an intracellular regulator (modifier) site of the Mg2+ transport protein. Binding of Mg2+ to the regulator site may be enhanced by phosphorylation and may induce an allosteric a transformation of the Mg2+ transport protein. In consequence, the selectivity filter can bind 2 extracellular Na+ in exchange for 1 Mg2+ bound to the selectivity filter. Thereafter, the 2 bound Na+ can be exchanged for 1 intracellular Mg2+ which in rum is exchanged for 2 extracellular Na+, yielding net Mg2+ efflux via Na+/Mg2+ antiport. In rat erythrocytes, this mechanism can be changed to net Mg2+ influx via Na+/Mg2+ antiport by reversing the Na+ gradient.