Effect of the Transmembrane Gradient of Magnesium and Sodium on the Regulation of Cytosolic Free Magnesium Concentration in Human Platelets

1. To clarify the mechanism by which cytosolic free Mg²⁺ concentrations ([Mg²⁺]_i) are regulated in human platelets, we investigated platelet membrane permeability to Mg²⁺ by altering extracellular Mg²⁺ concentrations, and tested the existence of a Na⁺-Mg²⁺ exchanger by manipulating the transmembrane Na⁺ gradient.

2. Platelet [Mg²⁺], was 421 ± 52 μmol/l in healthy men. [Mg²⁺]; remained constant during a 120 min exposure to nominally zero (low) or 5 mmol/l (high) external Mg²⁺ concentrations.

3. Preincubation of platelets with 10⁻⁴ mol/l ouabain effectively decreased the transmembrane Na⁺ gradient. The ouabain-induced increase in [Mg²⁺], was statistically significant after 30 min of exposure (14.6 ± 2.0%) and reached 24.6 ± 4.5% after 60 min. Similarly, the replacement of extracellular Na⁺ with N-methyl-d-glucamine significantly increased [Mg²⁺]_i by 48.5 ± 3.9% and 78.8 ± 12.5%, respectively.

4. These results suggest that [Mg²⁺]_i is well controlled in the presence of large transmembrane Mg²⁺ concentration gradients, and a Na⁺-Mg²⁺ exchanger may be involved in the regulation of [Mg²⁺]_i in human platelets.