The acute effects of epidermal growth factor (EGF) on Mg2+ homeostasis were studied in differentiated BC3H1 myocytes. EGF produced a 48-fold stimulation of [3H]thymidine incorporation into quiescent serum-starved cells in the presence of Mg2+, whereas insulin had no effect on [3H]thymidine incorporation. The dose dependence of EGF-stimulated [3H]thymidine incorporation was similar to that of EGF stimulation of 28Mg2+ uptake. In cells loaded with the Mg(2+)-sensitive fluorescent indicator, Mag-fura-2, intracellular Mg2+ concentration ([Mg2+]i) increased after exposure to EGF after a 5-min lag; a similar lag was routinely observed before the stimulation of 28Mg2+ uptake by EGF. In control studies, cytosolic free Ca2+ levels and intracellular pH (pHi) were unchanged during 20 min of exposure to EGF. These results suggest that [Mg2+]i in BC3H1 cells is regulated by EGF. This regulation is not mediated by changes in pHi or intracellular Ca2+ concentration and may constitute an important event in the physiological response of these cells to EGF. The results are discussed within the context of cellular regulation of Mg2+ homeostasis.
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