Differential localization and operation of distinct Mg2+ transporters in apical and basolateral sides of rat liver plasma membrane

Abstract

Upon activation of specific cell signaling, hepatocytes rapidly accumulate or release an amount of Mg2+ equivalent to 10% of their total Mg2+ content. Although it is widely accepted that Mg2+ efflux is Na+- dependent, little is known about transporter identity and the overall regulation. Even less is known about the mechanism of cellular Mg2+ uptake. Using sealed and right-sided rat liver plasma membrane vesicles representing either the basolateral (bLPM) or apical (aLPM) domain, it was possible to dissect three different Mg2+ transport mechanisms based upon specific inhibition, localization within the plasma membrane, and directionality. The bLPM possesses only one Mg2+ transporter, which is strictly Na+-dependent, bi-directional, and not inhibited by amiloride. The aLPM possesses two separate Mg2+ transporters. One, similar to that in the bLPM because it strictly depends on Na+ transport, and it can be differentiated from that of the bLPM because it is unidirectional and fully inhibited by amiloride. The second is a novel Ca2+/Mg2+ exchanger that is unidirectional and inhibited by amiloride and imipramine. Hence, the bLPM transporter may be responsible for the exchange of Mg2+ between hepatocytes and plasma, and vice versa, shown in livers upon specific metabolic stimulation, whereas the aLPM transporters can only extrude Mg2+ into the biliary tract. The dissection of these three distinct pathways and, therefore, the opportunity to study each individually will greatly facilitate further characterization of these transporters and a better understanding of Mg2+ homeostasis.