Differential localization and operation of distinct Mg(2+) transporters in apical and basolateral sides of rat liver plasma membrane.
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 possible 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.
Cefaratti
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Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Romani
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Scarpa
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D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology; D013696:Temperature
D002352:Carrier Proteins; D000584:Amiloride; D012964:Sodium; D008274:Magnesium; D007099:Imipramine; D002118:Calcium