Upon activation of specific cell signaling, hepatocytes rapidly accumulate or release an amount of Mg 2؉ equivalent to 10% of their total Mg 2؉ content. Although it is widely accepted that Mg 2؉ efflux is Na ؉ -dependent, little is known about transporter identity and the overall regulation. Even less is known about the mechanism of cellular Mg 2؉ uptake. Using sealed and right-sided rat liver plasma membrane vesicles representing either the basolateral (bLPM) or apical (aLPM) domain, it was

more »

... sible to dissect three different Mg 2؉ transport mechanisms based upon specific inhibition, localization within the plasma membrane, and directionality. The bLPM possesses only one Mg 2؉ transporter, which is strictly Na ؉ -dependent, bi-directional, and not inhibited by amiloride. The aLPM possesses two separate Mg 2؉ 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 Ca 2؉ /Mg 2؉ exchanger that is unidirectional and inhibited by amiloride and imipramine. Hence, the bLPM transporter may be responsible for the exchange of Mg 2؉ between hepatocytes and plasma, and vice versa, shown in livers upon specific metabolic stimulation, whereas the aLPM transporters can only extrude Mg 2؉ 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 Mg 2؉ homeostasis.