Key result
Addition of 1 mM BDM, 15 mM Pi, or lowering Ca2+ to pCa 5.5 reduced isometric force by ~50%, but only BDM elicited a decrease of force and slowing with maintained stiffness similar to fatigued muscle.
Why the study?
It was unclear whether characteristics of muscle fatigue, such as force loss and altered resistance to stretch, are due to reduced intracellular Ca2+ and increased Pi altering cross-bridge kinetics.
Muscle fatigue characteristics cannot be fully mimicked by reduced calcium or increased inorganic phosphate alone, suggesting a complex combination of factors altering cross bridge kinetics.
BDM alone mimics fatigue-like mechanics in animal fibers; leaves open multifactorial cross-bridge mechanisms in human fatigue.
Background and Objectives: Muscle fatigue is characterised by (1) loss of force, (2) decreased maximal shortening velocity and (3) a greater resistance to stretch that could be due to reduced intracellular Ca2+ and increased Pi, which alter cross bridge kinetics. Materials and Methods: To investigate this, we used (1) 2,3-butanedione monoxime (BDM), believed to increase the proportion of attached but non-force-generating cross bridges; (2) Pi that increases the proportion of attached cross bridges, but with Pi still attached; and (3) reduced activating Ca2+. We used permeabilised rat soleus fibres, activated with pCa 4.5 at 15 °C. Results: The addition of 1 mM BDM or 15 mM Pi, or the lowering of the Ca2+ to pCa 5.5, all reduced the isometric force by around 50%. Stiffness decreased in proportion to isometric force when the fibres were activated at pCa 5.5, but was well maintained in the presence of Pi and BDM. Force enhancement after a stretch increased with the length of stretch and Pi, suggesting a role for titin. Maximum shortening velocity was reduced by about 50% in the presence of BDM and pCa 5.5, but was slightly increased by Pi. Neither decreasing Ca2+ nor increasing Pi alone mimicked the effects of fatigue on muscle contractile characteristics entirely. Only BDM elicited a decrease of force and slowing with maintained stiffness, similar to the situation in fatigued muscle. Conclusions: This suggests that in fatigue, there is an accumulation of attached but low-force cross bridges that cannot be the result of the combined action of reduced Ca2+ or increased Pi alone, but is probably due to a combination of factors that change during fatigue.
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Degens et al. (2020) studied Muscle fatigue. 2,3-butanedione monoxime (BDM), increased Pi, and reduced Ca2+ vs. pCa 4.5 (baseline) was evaluated on Isometric force, stiffness, and maximum shortening velocity. Addition of 1 mM BDM, 15 mM Pi, or lowering Ca2+ to pCa 5.5 reduced isometric force by ~50%, but only BDM elicited a decrease of force and slowing with maintained stiffness similar to fatigued muscle.
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