Ionized magnesium in the homeostasis of cells: intracellular threshold for Mg(2+) in human platelets

The role of extracellular magnesium ions in the homeostasis of intracellular ionized magnesium ([Mg(2+)](i)) in human platelets was studied. For media containing 0.00 to 0.60 mmol/l of extracellular ionized magnesium ([Mg(2+)](o)), the mean [Mg(2+)](i) fluctuated between 533 and 760 micromol/l. As the [Mg(2+)](o) was increased to 1.5 mmol/l, the [Mg(2+)](i) increased proportionately and peaked at 1470.1 micromol/l. Additional increase in the [Mg(2+)](o) from 1.50 to 6.00 mmol/l resulted in decreased [Mg(2+)](i) until it equilibrated between 739 and 776 micromol/l. The influx of Mg(2+) at [Mg(2+)](o) of 0.60 and 1.50 mmol/l was studied using verapamil, a calcium channel inhibitor, and ouabain, an inhibitor of the Na/K pump, respectively. The verapamil (25 mmol/l) blocking experiments resulted in a 92.4% inhibition of the Mg(2+) influx into the platelet at a [Mg(2+)](o) of 1.50 mmol/l. Ouabain (0.5 and 2.5 mmol/l) showed an enhancement effect on the influx of Mg(2+) at [Mg(2+)](o) of 0.60 mmol/l and no effect at 1.50 mmol/l. The effect of verapamil indicates that ion channels that are homologous to calcium ion channels may be involved in the influx of Mg(2+) into the platelets. The inhibition of Mg(2+) influx for [Mg(2+)](o) greater than 1.50 mmol/l may illustrate a protective mechanism that attempts to maintain the viability of platelets at abnormally high [Mg(2+)](o). These results suggest that there is an intracellular Mg(2+) threshold of 1500 micromol/l, above which an active mechanism prevents further influx of Mg(2+).