Metabolic and nonmetabolic components of fatigue monitored with 31P-NMR

The goal of this study was to determine the roles of metabolic and nonmetabolic factors in muscle fatigue. Rat gastrocnemius muscles were fatigued by stimulation of the nerve (n = 6) or muscle (n = 4, after 2 days of denervation). 31Phosphorus nuclear magnetic resonance spectroscopy was used to measure levels of intracellular inorganic phosphate (Pi) and hydrogen ions (H+) (which are thought to inhibit contraction) and the high-energy phosphates, phosphocreatine (PCr), and ATP. For both indirect and direct stimulation, with fatigue to approximately 60% initial tetanic force, [Pi] increased from approximately 3.5 mmol/L to approximately 20 mmol/L and [PCr] decreased from approximately 27 mmol/L to approximately 9 mmol/L. However, with continued fatigue to 25-35% initial tetanic force, neither [Pi] or [PCr] changed further. [ATP] and pH changed only slightly during fatigue. The results are consistent with early fatigue arising from metabolic inhibition of contraction; but later fatigue arising independent of metabolites, due to impaired activation beyond the neuromuscular junction.