Prolonged force depression after mechanically demanding contractions is largely independent of Ca ²⁺ and reactive oxygen species

Abstract

Increased production of reactive oxygen/nitrogen species (ROS) and impaired cellular Ca handling are implicated in the prolonged low-frequency force depression (PLFFD) observed in skeletal muscle after both metabolically and mechanically demanding exercise. Metabolically demanding high-intensity exercise can induce PLFFD accompanied by ROS-dependent fragmentation of the sarcoplasmic reticulum Ca release channels, the ryanodine receptor 1s (RyR1s). We tested whether similar changes occur after mechanically demanding eccentric contractions. Human subjects performed 100 repeated drop jumps, which require eccentric knee extensor contractions upon landing. This exercise caused a major PLFFD, such that maximum voluntary and electrically evoked forces did not recover within 24 h. Drop jumps induced only minor signs of increased ROS, and RyR1 fragmentation was observed in only 3 of 7 elderly subjects. Also, isolated mouse muscle preparations exposed to drop-jump-mimicking eccentric contractions showed neither signs of increased ROS nor RyR1 fragmentation. Still, the free cytosolic [Ca] during tetanic contractions was decreased by ∼15% 1 h after contractions, which can explain the exaggerated force decrease at low-stimulation frequencies but not the major frequency-independent force depression. In conclusion, PLFFD caused by mechanically demanding eccentric contractions does not involve any major increase in ROS or RyR1 fragmentation.-Kamandulis, S., de Souza Leite, F., Hernandez, A., Katz, A., Brazaitis, M., Bruton, J. D., Venckunas, T., Masiulis, N., Mickeviciene, D., Eimantas, N., Subocius, A., Rassier, D. E., Skurvydas, A., Ivarsson, N., Westerblad, H. Prolonged force depression after mechanically demanding contractions is largely independent of Ca and reactive oxygen species.

Elongated mitochondrial constrictions and fission in muscle fatigue

“…Additionally, changes in Mg levels (Westerblad and Allen, 1992;Nassar-Gentina et al, 1981), accumulation of lactate from glycolysis and of inorganic phosphate from breakdown of creatine phosphate (Allen and Westerblad, 2001), and in more extreme cases, changes in the rate of ATP hydrolysis (Nagasser et al, 1992) and reduction or failure to release calcium (Westerblad and Allen, 1993) can occur. Production and accumulation of active oxygen species has been more recently added to the list of fatiguerelated alterations (Cheng et al, 2016;Kamandulis et al, 2017). Oxygen demand is also altered during strong exercise; it may increase more than 20-fold in human skeletal muscle during intense exercise (Bangsbo, 2000).…”

Low frequency fatigue and changes in muscle fascicle length following eccentric exercise of the knee extensors

“…This is far shorter than the damaging protocol of Balnave and Allen and even shorter than the 125% used in their less damaging protocol, suggesting it is unlikely that the reduced 20/100 ratio was due to a reduction in calcium sensitivity. In addition, Kamandulis et al (2017) examined the function of myofibrils isolated from muscle biopsies taken from subjects showing considerable LFF and loss of torque, 24 h after a prolonged series of drop jumps but found no major changes in the force developed in response to Ca 2+ , consistent with changes in muscle function being due to problems of calcium release rather than calcium sensitivity. This observation, together with the fact that in the animal work of Warren et al (1993) the initial force loss was largely restored with caffeine, which implicates calcium release rather than changes in sensitivity, suggests that it is the release mechanism which is affected in this early phase of damage.…”

“…In addition, Kamandulis et al. () examined the function of myofibrils isolated from muscle biopsies taken from subjects showing considerable LFF and loss of torque, 24 h after a prolonged series of drop jumps but found no major changes in the force developed in response to Ca 2+ , consistent with changes in muscle function being due to problems of calcium release rather than calcium sensitivity. This observation, together with the fact that in the animal work of Warren et al.…”

“…Skeletal muscle that has been subjected to eccentric exercise shows a disproportionate loss of force when electrically stimulated at low, compared to higher, frequencies (Davies & White, 1981;Kamandulis et al, 2017;Newham, Jones, & Clarkson, 1987;Skurvydas et al, 2016). This feature is relatively slow to recover and is often described as long lasting or low frequency fatigue (LFF) and may be a consequence of reduced calcium release in response to individual action potentials (Balnave & Allen, 1995;Edwards, Hill, Jones, & Merton, 1977) indicating some deficit in the mechanism of excitationcontraction (EC) coupling.…”

The effects of betalain-rich concentrate supplementation in attenuating muscle damage following eccentric exercise

“…Because eccentric contractions preferentially damage fast-twitch muscle fibres (Brockett et al, 2002), the free radical scavenging properties of betalains could theoretically increase force production independent of muscle damage. A recent study by Kamandulis et al (2017) reported prolonged reductions in MVC independent of increases in ROS immediately and 24 hr following 100 drop jumps. However, ROS production has been found to increase in the days following acute eccentric muscle damage.…”