Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells

Dystrophic skeletal muscle cells from Duchenne muscular dystrophy (DMD) patients and mdx mice exhibit elevated cytosolic Ca2+ concentrations ([Ca2+]c). Pretreatment of mdr myotubes for 6-12 days with creatine (20 mM) decreased the elevation in [Ca2+]c induced by either high extracellular Ca2+ concentrations or hypo-osmotic stress to control levels. 45Ca2+ influx measurements suggest that creatine lowered [Ca2+]c by stimulating sarcoplasmic reticulum Ca2+-ATPase. Creatine pretreatment increased levels of phosphocreatine but not ATP. Furthermore, myotube formation and survival were significantly enhanced by creatine pretreatment. Therefore, creatine supplementation may be useful for treatment of DMD.