Stretch Activation During Fatigue Improves Relative Force Production In Fast-contracting Mouse Skeletal Muscle Fibers

Stretch activation (FSA) is the delayed increase in muscle fiber force following a rapid stretch and may improve skeletal muscle performance during activities with repetitive cyclical contractions, such as walking or running. Although historically considered minimal compared to cardiac or insect flight muscle, our recent work shows greater levels of inorganic phosphate (Pi) improves relative force production (FSA/F0, F0 = calcium-activated force) in soleus skeletal muscle fibers. As peripheral muscular fatigue includes Pi accumulation, our results suggest FSA improves force production in fatigued skeletal muscle. PURPOSE: To determine the effects of fatigue (low pH, high Pi) at low and high calcium (Ca2+) concentrations on FSA and FSA/F0 in myosin heavy chain (MHC) I, IIA, IIX, and IIB expressing fibers compared to control (high Ca2+ at resting levels of pH and Pi). METHODS: Single fibers from soleus and extensor digitorum longus muscles of female C57BL/6NJ mice were stretched 0.5% of their muscle length at normal and fatigued pH (7.0, 6.2) and Pi (5, 30 mM) as well as at high (pCa 4.5, pCa = -log([Ca2+]) and low (pCa 5.1) Ca2+ concentrations. RESULTS: F0 decreased from control to high calcium fatigue to low calcium fatigue conditions for all MHC isoforms, as expected. In MHC IIX and IIB fibers, FSA occurred under all conditions and FSA/F0 increased from control (17-20%) to high calcium fatigue (32-35%, p < 0.001) to low calcium fatigue (42-44%, p < 0.001 vs both). In MHC IIA fibers, FSA/F0 increased similarly to MHC IIX and IIB fibers in control (14%) and high calcium fatigue (32%, p < 0.001) but did not increase further under low calcium fatigue (35%, p < 0.001 vs control). For MHC I fibers, FSA/F0 was low in control (4%) and was non-existent in high and low calcium fatigue, as no discernable FSA was observed. CONCLUSION: Stretch activation in fast-contracting muscle fibers is a significant modulator of force production under fatiguing conditions. This response may be due to the reversal and re-occurrence of myosin power strokes in the presence of a stretch and Pi. This mechanism would reduce fatigue effects in locomotor activities, when the antagonistic muscle rapidly stretches the agonist muscle, if the delayed increase in force due to stretch activation happens when the agonist muscle is shortening.