Free Mg(2+ )concentration in the calf muscle of glycogen phosphorylase and phosphofructokinase deficiency patients assessed in different metabolic conditions by (31)P MRS

BACKGROUND: The increase in cytosolic free Mg(2+ )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 ((31)P MRS). To investigate in vivo to what extent the homeostasis of intracellular free Mg(2+ )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 (31)P MRS the cytosolic pH and free magnesium concentration ([Mg(2+)]) 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 [Mg(2+)] higher than the value found in control subjects. During exercise and recovery the McArdle patients did not show any significant change in free [Mg(2+)], while both PFK patients showed decreased free [Mg(2+)] and a remarkable accumulation of phosphomonoesters (PME). During initial recovery both McArdle patients showed a small increase in free [Mg(2+)] while in PFK patients the pattern of free [Mg(2+)] was related to the rate of PME recovery. CONCLUSION: i) homeostasis of free [Mg(2+)] in human skeletal muscle is strongly linked to pH as shown by patients' [Mg(2+)] pattern during exercise; ii) the pattern of [Mg(2+)] during exercise and post-exercise recovery in both PFK patients suggests that [Mg(2+)] is influenced by the accumulation of the phosphorylated monosaccharide intermediates of glycogenolysis, as shown by the increased PME peak signal. iii) (31)P MRS is a suitable tool for the in vivo assessment of free cytosolic [Mg(2+)] in human skeletal muscle in different metabolic conditions;