Ionized magnesium in the homeostasis of cells: Intracellular threshold for Mg²⁺ in human platelets

The role of extracellular magnesium ions in the homeostasis of intracellular ionized magnesium ([Mg²⁺]_i) in human platelets was studied. For media containing 0.00 to 0.60 mmol/l of extracellular ionized magnesium ([Mg²⁺]_o), the mean [Mg²⁺]_i fluctuated between 533 and 760 μmol/l. As the [Mg²⁺]_o was increased to 1.5 mmol/l, the [Mg²⁺]_i increased proportionately and peaked at 1470.1 μmol/l. Additional increase in the [Mg²⁺]_o from 1.50 to 6.00 mmol/l resulted in decreased [Mg²⁺]_i until it equilibrated between 739 and 776 μmol/l. The influx of Mg²⁺ at [Mg²⁺]_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 Mg²⁺ influx into the platelet at a [Mg²⁺]_o of 1.50 mmol/l. Ouabain (0.5 and 2.5 mmol/l) showed an enhancement effect on the influx of Mg²⁺ at [Mg²⁺]_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 Mg²⁺ into the platelets. The inhibition of Mg²⁺ influx for [Mg²⁺]_o greater than 1.50 mmol/l may illustrate a protective mechanism that attempts to maintain the viability of platelets at abnormally high [Mg²⁺]_o. These results suggest that there is an intracellular Mg²⁺ threshold of 1500 μmol/l, above which an active mechanism prevents further influx of Mg²⁺.