Free Mg2+ concentration in the calf muscle of glycogen phosphorylase and phosphofructokinase deficiency patients assessed in different metabolic conditions by 31P MRS

BACKGROUND The increase in cytosolic free Mg2+ occurring during exercise and initial recovery in human skeletal muscle is matched by a decrease in cytosolic pH as shown by in vivo phosphorus magnetic resonance spectroscopy (31P MRS). To investigate in vivo to what extent the homeostasis of intracellular free Mg2+ is linked to pH in human skeletal muscle, we studied patients with metabolic myopathies due to different disorders of glycogen metabolism that share a lack of intracellular acidification during muscle exercise. METHODS We assessed by 31P MRS the cytosolic pH and free magnesium concentration ([Mg2+]) in calf muscle during exercise and post-exercise recovery in two patients with McArdle's disease with muscle glycogen phosphorylase deficiency (McArdle), and two brothers both affected by Tarui's disease with muscle phosphofructokinase deficiency (PFK). RESULTS All patients displayed a lack of intracellular acidosis during muscle exercise. At rest only one PFK patient showed a [Mg2+] higher than the value found in control subjects. During exercise and recovery the McArdle patients did not show any significant change in free [Mg2+], while both PFK patients showed decreased free [Mg2+] and a remarkable accumulation of phosphomonoesters (PME). During initial recovery both McArdle patients showed a small increase in free [Mg2+] while in PFK patients the pattern of free [Mg2+] was related to the rate of PME recovery. CONCLUSION i) homeostasis of free [Mg2+] in human skeletal muscle is strongly linked to pH as shown by patients' [Mg2+] pattern during exercise; ii) the pattern of [Mg2+] during exercise and post-exercise recovery in both PFK patients suggests that [Mg2+] is influenced by the accumulation of the phosphorylated monosaccharide intermediates of glycogenolysis, as shown by the increased PME peak signal. iii) 31P MRS is a suitable tool for the in vivo assessment of free cytosolic [Mg2+] in human skeletal muscle in different metabolic conditions.