Regulation of intracellular magnesium concentration by sodium-magnesium exchange

Abstract

Magnesium must be actively extruded from the cell interior to keep cytoplasmic free Mg²⁺ concentration of about 1 mM or lower. One candidate for such active Mg²⁺ extrusion mechanisms is the Na⁺-Mg²⁺ exchange that has been postulated in many types of cells, including cardiac myocytes. However, the genes encoding the Mg²⁺ transporters have not yet been identified, and the Mg²⁺ transport is only poorly characterized. In this presentation, we will focus on modulation of the Mg²⁺ transport by membrane potential and intracellular/extracellular concentrations of Mg (Mg²⁺_i/Mg²⁺_o) and Na (Na⁺_i/Na⁺_o) ions in cardiac myocytes. We measured Mg²⁺_i of single ventricular myocytes of rat using the fluorescent Mg²⁺ indicator furaptra (mag-fura-2). After the cells were loaded with Mg²⁺ by incubation in the solution containing high Mg²⁺ concentration, and the rate of fall in Mg²⁺_i upon reduction of Mg²⁺_o was analyzed as an index of the Mg²⁺ efflux rate. Cell membrane depolarization slightly but significantly facilitated the Mg²⁺ efflux in the cells patch-clamped with the pipette containing amphotericin B. Activity of the Mg²⁺ transport was found to require extracellular Na⁺ with a half maximum Na⁺_o of ~50 mM, but was inhibited by intracellular Na⁺ with a half inhibitory Na⁺_i of ~40 mM. The transport was half-maximally activated by ~1.5 mM Mg²⁺_i, and was half-inhibited by ~10 mM Mg²⁺_o. In the light of these and other findings, contribution of the Na⁺-Mg²⁺ exchange as a major Mg²⁺ efflux pathway and intracellular Mg²⁺ buffering/sequestration to cellular Mg²⁺ regulation will be reviewed and discussed. [Jpn J Physiol 54 Suppl:S36 (2004)]