The metabolic causes of slow relaxation in fatigued human skeletal muscle.

1. The relationship between slowing of relaxation and changes of intracellular pH and phosphorous metabolites has been examined in human skeletal muscle during the development of fatigue and subsequent recovery. Results obtained with normal subjects have been compared with those from a subject with myophosphorylase deficiency (MPD) who produced no H+ from glycolysis during exercise and therefore afforded the opportunity of assessing the role of H+ in the slowing of relaxation. 2. Subjects fatigued the first dorsal interosseous muscle in a stepwise fashion under ischaemic conditions, with intervals between the fatiguing contractions during which the relaxation rate was measured from brief tetanic contractions and the muscle phosphorous metabolites and pH were measured by nuclear magnetic resonance spectroscopy. 3. After 21 s maximal voluntary contraction under ischaemic conditions, relaxation in the MPD subject slowed to approximately 50% of the rate in the fresh muscle at a time when the intramuscular pH had not changed. This demonstrates that there is a mechanism causing slowing of relaxation that is independent of H+ accumulation. 4. The normal subjects showed a slow recovery of relaxation compared to the MPD subject when the circulation was restored. The main difference in the intracellular metabolite concentrations between MPD and normal subjects at this time was that, for the latter, the pH remained low (around 6.5) for at least 60 s after the circulation was restored. The results suggest that the slow recovery is a consequence of continuing acidosis, i.e. the existence of a pH-dependent mechanism of slowing. 5. The existence of a pH-dependent mechanism was further indicated by the fact that for the normal subjects, for a similar intracellular concentration of phosphocreatine, relaxation of the recovering muscle was approximately half that of the fatiguing muscle. This was at a time when the pH of the recovering muscle was 0.3-0.4 units less than in the partially fatigued muscle. 6. The results show that in normal muscle there are at least two processes that lead to slow relaxation in fatigued muscle: one due to H+ accumulation, the other being independent of H+.