Are Force Enhancement after Stretch and Muscle Fatigue Due to Effects of Elevated Inorganic Phosphate and Low Calcium on Cross Bridge Kinetics?

Abstract

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.

Age-Related Skeletal Muscle Dysfunction Is Aggravated by Obesity: An Investigation of Contractile Function, Implications and Treatment

“…Obesity effects on eccentric muscle function may, like in ageing, not be analogous to those seen for concentric and isometric function. Mechanistically, eccentric force production differs from other contractility modes and is believed to be reliant on a high rate of reattachment of stretched cross-bridges [ 144 ] and on the active stiffening of the giant protein titin [ 145 , 146 , 147 ]. Obese individuals likely have a greater reliance on high-intensity eccentric contractions given the requirement to control a larger load.…”

Blood-Based Markers for Skeletal and Cardiac Muscle Function in Eventing Horses before and after Cross-Country Rides and How They Are Influenced by Plasma Volume Shift

“…Inorganic phosphates drop 30 min after exercise. An accumulation of inorganic phosphates in the muscles, which seems to contribute to peripheral fatigue [62], could be related to a drop in concentration in the blood, although only small amounts of inorganic phosphate circulate in the blood [62][63][64][65]. It could be hypothesized that the plasma dissolved inorganic phosphate is used to produce Adenosine-Triphosphate (ATP) via phosphorylation and the breakdown products then accumulate in the muscle cells, causing fatigue [63].…”