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

Abstract

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.