Magnesium Preserves Calcium Homeostasis and Contributes to Protect Myotubes from Inflammation-Induced Damage

Magnesium (Mg2+) is a key regulator of cellular biochemical processes and an essential cofactor in skeletal muscle physiology. Although Mg2+ deficiency has been linked to reduced muscle strength, its role in the regulation of calcium (Ca2+) signaling and in inflammation remains incompletely understood. In this study, we examined the effects of Mg2+ availability using the murine myoblast cell line C2C12. Cells were differentiated under low, normal, or high Mg2+ conditions, and myotube formation, intracellular Ca2+ fluxes, and resistance to inflammatory stimuli were assessed. Mg2+ deficiency impaired myotube differentiation, while Mg2+ supplementation preserved Ca2+ response during stimulation and contributed to protect myotubes against inflammation-induced damage. Collectively, these findings highlight a dual role of Mg2+ in sustaining functional performance under repeated stress and protecting myotubes against inflammatory injury. This study supports the importance of adequate dietary Mg2+ intake as a potential strategy to mitigate muscle loss associated with aging and chronic inflammation.