MODULATION OF ERYTHROCYTE POTASSIUM-CHLORIDE COTRANSPORT, POTASSIUM CONTENT, AND DENSITY BY DIETARY MAGNESIUM INTAKE IN TRANSGENIC SAD MOUSE

Prevention of erythrocyte dehydration is a potential therapeutic strat egy for sickle cell disease, Increasing erythrocyte magnesium (Mg) cou ld inhibit sickle cell dehydration by increasing chloride (CI) and wat er content and by inhibiting potassium chloride (K-CI) cotransport. In transgenic SAD 1 and (control) C57BL/6 normal mice, we investigated t he effect of 2 weeks of diet with either low Mg (6 +/- 2 mg/kg body we ight/d) or high Mg (1,000 +/- 20 mg/kg body weight/d), in comparison w ith a diet of standard Mg (400 +/- 20 mg/kg body weight/d). The high-M g diet increased SAD 1 erythrocyte Mg and K contents and reduced K-CI cotransport activity, mean corpuscular hemoglobin concentration (MCHC) , cell density, and reticulocyte count. SAD 1 mice treated with low-Mg diet showed a significant reduction in erythrocyte Mg and K contents and increases in K-CI cotransport, MCHC, cell density, and reticulocyt e counts. In SAD 1 mice, hematocrit (Hct) and hemoglobin (Hb) decrease d significantly with low Mg diet and increased significantly with high -Mg diet, The C57BL/6 controls showed significant changes only in eryt hrocyte Mg and K content, and K-CI cotransport activities, similar to those observed in SAD 1 mice. Thus, in the SAD 1 mouse, changes in die tary Mg modulate K-CI cotransport, modify erythrocyte dehydration, and ultimately affect Hb levels. (C) 1996 by The American Society of Hema tology.