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

Abstract

SUMMARY1. 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 t Present address:

Changes of intracellular pH due to repetitive stimulation of single fibres from mouse skeletal muscle.

“…This conclusion is in agreement with recent results from fatigued human muscle (Cady, Elshove, Jones & Moll, 1989). The mechanisms by which these processes cause slowed relaxation are not fully understood.…”

Skeletal Muscle Fatigue: Cellular Mechanisms

“…Nevertheless, acidification of mouse FDB fibers at ϳ30°C (close to the ambient tem-perature of this superficially located muscle) caused a significant decrease in the rate of relaxation both in the unfatigued and the fatigued state (71,478). Thus it appears that acidification contributes to the slowing of relaxation in fatigued mammalian muscle even at physiological temperatures, which agrees with in vivo human muscle results (77).…”

Muscle cell function during prolonged activity: cellular mechanisms of fatigue

“…Fig. 9; Cady et al 1989a). The linear phase of mechanical relaxation slows by a factor of about 2, but the rapid decline of [Ca2+]i shows only a small reduction in rate.…”

“…A further factor is whether or not the muscle develops an acidosis during the stimulus protocol. For instance, Cady, Elshove, Jones & Moll (1989a) (Klein, Kovacs, Simon & Schneider, 1991). (In frog muscles there is a transient increase in [Ca2+]i between phases (ii) and (iii) (Cannell, 1986).)…”

“…Nevertheless the correlation between slowing of relaxation and ATP turnover remains, and is consistent with the hypothesis that slowing of cross-bridge detachment contributes to slowing of relaxation. A useful distinction, emphasized by Cady et al (1989a), is that there are (at least) two distinct mechanisms involved in the slowing of relaxation during fatigue. Intracellular acidosis causes slowing of relaxation (e.g.…”