Fachbereich Veterinärmedizin



    Human gene SLC41A1 encodes for the Na+/Mg²+ exchanger (2012)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Kolisek, Martin
    Nestler, Axel
    Vormann, Jürgen
    Schweigel-Röntgen, Monika
    American journal of physiology / Cell physiology; 302(1) — S. C318–C326
    ISSN: 0363-6143
    DOI: 10.1152/ajpcell.00289.2011
    Pubmed: 22031603
    Institut für Veterinär-Physiologie

    Oertzenweg 19 b
    14163 Berlin
    Tel.+49 30 838 62600 Fax.+49 30 838-62610

    Abstract / Zusammenfassung

    Magnesium (Mg(2+)), the second most abundant divalent intracellular cation, is involved in the vast majority of intracellular processes, including the synthesis of nucleic acids, proteins, and energy metabolism. The concentration of intracellular free Mg(2+) ([Mg(2+)](i)) in mammalian cells is therefore tightly regulated to its optimum, mainly by an exchange of intracellular Mg(2+) for extracellular Na(+). Despite the importance of this process for cellular Mg(2+) homeostasis, the gene(s) encoding for the functional Na(+)/Mg(2+) exchanger is (are) still unknown. Here, using the fluorescent probe mag-fura 2 to measure [Mg(2+)](i) changes, we examine Mg(2+) extrusion from hSLC41A1-overexpressing human embryonic kidney (HEK)-293 cells. A three- to fourfold elevation of [Mg(2+)](i) was accompanied by a five- to ninefold increase of Mg(2+) efflux. The latter was strictly dependent on extracellular Na(+) and reduced by 91% after complete replacement of Na(+) with N-methyl-d-glucamine. Imipramine and quinidine, known unspecific Na(+)/Mg(2+) exchanger inhibitors, led to a strong 88% to 100% inhibition of hSLC41A1-related Mg(2+) extrusion. In addition, our data show regulation of the transport activity via phosphorylation by cAMP-dependent protein kinase A. As these are the typical characteristics of a Na(+)/Mg(2+) exchanger, we conclude that the human SLC41A1 gene encodes for the Na(+)/Mg(2+) exchanger, the predominant Mg(2+) efflux system. Based on this finding, the analysis of Na(+)/Mg(2+) exchanger regulation and its involvement in the pathogenesis of diseases such as Parkinson's disease and hypertension at the molecular level should now be possible.