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This Article Full Text Full Text (PDF) All Versions of this Article: 94/1/441    most recent 01221.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Günzel, D. Articles by Schlue, W.-R. Search for Related Content PubMed PubMed Citation Articles by Günzel, D. Articles by Schlue, W.-R.

Mg²⁺-Malate Co-Transport, a Mechanism for Na⁺-Independent Mg²⁺ Transport in Neurons of the Leech Hirudo medicinalis

¹Institut für Neurobiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf; and ²Institut für Klinische Physiologie, Charité, Berlin, Germany

Submitted 30 November 2004; accepted in final form 18 March 2005

Mg²⁺-extrusion from Mg²⁺-loaded neurons of the leech, Hirudo medicinalis, is mediated mainly by Na⁺/Mg²⁺ antiport. However, in a number of leech neurons, Mg²⁺ is extruded in the nominal absence of extracellular Na⁺, indicating the existence of an additional, Na⁺-independent Mg²⁺ transport mechanism. This mechanism was investigated using electrophysiological and microfluorimetrical techniques. The rate of Na⁺-independent Mg²⁺ extrusion from Mg²⁺-loaded leech neurons was found to be independent of extracellular Ca²⁺, K⁺, NO₃^–, HCO₃^–, SO₄^2–, HPO₄^2–, and of intra- and extracellular pH. Na⁺-independent Mg²⁺ extrusion was not inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), furosemide, ouabain, vanadate, iodoacetate, 4-amino-hippurate, or -cyano-4-hydroxycinnamate and was not influenced by changes in the membrane potential in voltage-clamp experiments. Na⁺-independent Mg²⁺ extrusion was, however, inhibited by the application of 2 mM probenecid, a blocker of organic anion transporters, suggesting that Mg²⁺ might be co-transported with organic anions. Extracellularly, of all organic anions tested (malate, citrate, lactate, -ketoglutarate, and 4-amino-hippurate) only high, but physiological, concentrations of malate (30 mM) had a significant inhibitory effect on Na⁺-independent Mg²⁺ extrusion. Intracellularly, iontophoretically injected malate, citrate, or fura-2, but not Cl^–, -ketoglutarate, glutamate, succinate, or urate, were stimulating Na⁺-independent Mg²⁺ extrusion from those neurons that initially did not extrude Mg²⁺ in Na⁺-free solutions. Our data indicate that Mg²⁺ is co-transported with organic anions, preferably with malate, the predominant extracellular anion in the leech. The proposed model implies that, under experimental conditions, malate drives Mg²⁺ extrusion, whereas under physiological conditions, malate is actively taken up, driven by Mg²⁺, so that malate can be metabolized.