Blocking the rise of intracellular calcium inhibits the growth of cells cultured in different concentrations of magnesium

Divalent cations, especially calcium and magnesium, have been shown to play an important regulatory role in endothelial and immune cells. To learn more about the interaction of these two metals in the regulation of cell growth, we altered the calcium/magnesium ratio by culturing human endothelial cells, macrophages, and T lymphocytes in media containing different concentrations of magnesium. We observed that the growth of the three cell types was retarded in low extracellular magnesium, and this retardation is particularly evident in highly proliferating cells. High concentrations of magnesium does not exert any effect on cell growth. When (i) calcium influx was blocked by adding the calcium antagonist verapamil, and (ii) calcium release from intracellular stores was inhibited by exposure to TMB-8, the growth of endothelial cells, macrophages, and T lymphocytes was inhibited. In particular, the release of calcium from intracellular stores seems to be more important than its influx in sustaining cell proliferation. Our results indicate that calcium plays a crucial role in mediating cell proliferation independently from the extracellular concentrations of magnesium.