Reduced cytosolic acidification during exercise suggests defective glycolytic activity in skeletal muscle of patients with Becker muscular dystrophy

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Abstract
Becker muscular dystrophy is an X-linked disorder due to mutations in the dystrophin gene, resulting in reduced size and/or content of dystrophin. The functional role of this subsarcolemmal protein and the biochemical mechanisms leading to muscle necrosis in Becker muscular dystrophy are still unknown. In particular, the role of a bioenergetic deficit is still controversial. In this study, we used 31P magnetic resonance spectroscopy (31P-MRS) to investigate skeletal muscle mitochondrial and glycolytic ATP production in vivo in 14 Becker muscular dystrophy patients. Skeletal muscle glycogenolytic ATP production, measured during the first minute of exercise, was similar in patients and controls. On the other hand, during later phases of exercise, skeletal muscle in Becker muscular dystrophy patients was less acidic than in controls, the cytosolic pH at the end of exercise being significantly higher in Becker muscular dystrophy patients. The rate of proton efflux from muscle fibres of Becker muscular dystrophy patients was similar to that of controls, pointing to a deficit in glycolytic lactate production as a cause of higher end-exercise cytosolic pH in patients. The maximum rate of mitochondrial ATP production was similar in muscle of Becker muscular dystrophy patients and controls. The results of this in vivo31P-MRS study are consistent with reduced glucose availability in dystrophin-deficient muscles.