Cytosolic pH buffering during exercise and recovery in skeletal muscle of patients with McArdle’s disease

Abstract

Cellular pH control is important in muscle physiology, and for interpretation of (31)P magnetic resonance spectroscopy (MRS) data. Cellular acidification in exercise results from coupled glycolytic ATP production mitigated by cytosolic buffering, 'consumption' of H(+) by phosphocreatine (PCr) breakdown, and membrane transport processes. Ex vivo methods for cytosolic buffer capacity are vulnerable to artefact, and MRS methods often require assumptions. (31)P MRS of early exercise, when pH increases unopposed by glycolysis, is conceptually simple, but limited in normal muscle by time resolution and signal-to-noise. A therapeutic trial (Martinuzzi A et al. Musc Nerve 37: 350-357, 2007) in McArdle's disease (glycogen phosphorylase deficiency), where pH does not decrease with exercise, offered the opportunity to test (31)P MRS data obtained throughout incremental plantar flexion exercise and recovery in ten McArdle's patients against the simple model of cellular pH control. Changes in pH, [Pi] and [PCr] throughout exercise and recovery were quantitatively consistent with mean +/- SEM buffer capacity of 10 +/- 1 mM/(pH unit), which was not significantly different from the control subjects under the initial-exercise conditions where the comparison could be made. The simple model of cellular acid-base balance therefore gives an adequate account of cellular pH changes during both exercise and recovery in McArdle's disease.

Quantification of skeletal muscle mitochondrial function by 31P magnetic resonance spectroscopy techniques: a quantitative review

“…One is cellular pH homeostasis, which involves the processes of what might be termed H + production, consumption, buffering and efflux (Kemp et al . , , ). The other is muscle mitochondrial function, in the sense of oxidative ATP synthesis, its regulation in relation to ATP demand, and its pathophysiology.…”

“…, Kemp et al . ) presumably reflect impaired glycogenolytic supply of pyruvate for oxidation, illustrating clearly the need for caution in interpreting MMMF.…”

31P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations

“…For example, if glycogenolysis is absent, as in the metabolic disorder McArdle's disease (muscle glycogen phosphorylase deficiency), exercise produces a characteristic and quantifiable pattern of 31 P MRS abnormalities. 126 If more subtle changes in glycogenolysis are of interest, it makes sense to study the muscle in ischaemic exercise, where there is no oxidative contribution to ATP synthesis. 26 Another simple example: when peripheral vascular disease impairs the ability to clear acid from the muscle cell, pH recovery after exercise is slowed, 122 pH and PCr recovery kinetics can be used to estimate absolute rates of post-exercise acid efflux 14,21 but this has rarely been exploited in disease.…”

“…In some cases the (patho)physiological interpretation is straightforward. For example, if glycogenolysis is absent, as in the metabolic disorder McArdle's disease (muscle glycogen phosphorylase deficiency), exercise produces a characteristic and quantifiable pattern of 31 P MRS abnormalities 126 . If more subtle changes in glycogenolysis are of interest, it makes sense to study the muscle in ischaemic exercise, where there is no oxidative contribution to ATP synthesis 26 .…”

In-vivo 31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism

“…Unlike in static investigations, a low number of transients (commonly just one) is used in dynamic examinations due to the high temporal resolution required (on the order of seconds). Through the measurement of post-exercise recovery, dynamic 31 P-MRS allows direct investigation of the pH homeostasis, as well as of the oxidative ATP synthesis regulation in relation to ATP demand [6], [63], [96], [97]. Therefore, if technically possible, dynamic 31 P-MRS is the method of choice for the investigation of the mitochondrial metabolism of skeletal muscle in vivo.…”