DOES CENTRAL FATIGUE LIMIT MUSCLE FORCE GENERATION CAPACITY DURING FATIGUE?

There is general agreement on peripheral factors of muscle fatigue that develop within the muscle and impair muscle fiber contractile mechanisms and muscle performance. Central factors of muscle fatigue that arise within the central nervous system have also been suggested to influence muscle force during fatigue. However, no direct empirical evidence of their influence on muscle force capacity has yet been reported. We used a force model to investigate whether peripheral factors are sufficient to explain the loss of muscle force generation capacity during fatiguing submaximal voluntary contractions that is commonly attributed to central factors. Our simulations showed that the force behavior during fatigue could be explained solely by peripheral factors. These data raise concerns about the influence of central factors on muscle force generation capacity during fatigue

Muscle Unloading Induced Sex Specific Neurophysiological and Myofiber Profile Adaptations

Muscle unloading affects a muscle’s ability to produce a contractile force and it affects the muscle’s endurance. The objective of this project was to investigate the differences between males and females and their neurophysiological adaptations to hindlimb suspension, an effective model of muscle unloading. Thirty nine young adult Wistar rats were divided into the following four groups: 1) male control, 2) female control, 3) male unloading, 4) female unloading. The unloading groups were subjected to a hindlimb suspension model. Soleus muscles were surgically removed to quantify neuromuscular function, and fluorescent fiber type staining was performed to quantify the cross-sectional area and fiber type composition. By using different stimulation protocols, muscle contraction was induced either directly or indirectly (via motor nerve terminals) and muscular force was quantified by a force transducer. Flourescent staining was used to image type I and type II fibers. The results showed that over a 5 minute stimulation protocol, muscle fatigue was greater during indirect stimulation than direct stimulation, indicating that the motor neuron fatigues at a faster rate than the muscle fibers it innervates. Hindlimb suspension affected the females more than the males whether the muscle was stimulated directly or by the nerve. Unloading significantly increased the neuromuscular block over the five minute fatigue train only in the females. There was significant atrophy in the unloaded groups, but no sex-specific significant differences and no fiber type transitions. In summary, the muscle fatigue is likely due to fatigue in the neuron’s ability to stimulate the muscle, and females are more affected by the hindlimb suspension than males. There was also unloading induced atrophy but it was not sex specific

A novel approach for determining fatigue resistances of different muscle groups in static cases

In ergonomics and biomechanics, muscle fatigue models based on maximum endurance time (MET) models are often used to integrate fatigue effect into ergonomic and biomechanical application. However, due to the empirical principle of those MET models, the disadvantages of this method are: 1) the MET models cannot reveal the muscle physiology background very well; 2) there is no general formation for those MET models to predict MET. In this paper, a theoretical MET model is extended from a simple muscle fatigue model with consideration of the external load and maximum voluntary contraction in passive static exertion cases. The universal availability of the extended MET model is analyzed in comparison to 24 existing empirical MET models. Using mathematical regression method, 21 of the 24 MET models have intraclass correlations over 0.9, which means the extended MET model could replace the existing MET models in a general and computationally efficient way. In addition, an important parameter, fatigability (or fatigue resistance) of different muscle groups, could be calculated via the mathematical regression approach. Its mean value and its standard deviation are useful for predicting MET values of a given population during static operations. The possible reasons influencing the fatigue resistance were classified and discussed, and it is still a very challenging work to find out the quantitative relationship between the fatigue resistance and the influencing factors

Muscle Fatigue from the Perspective of a Single Crossbridge

The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H+). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process. This seems to be due, in part, to their direct effect on muscle’s molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosin’s ability to move actin. Indeed, recent work using a single molecule laser trap assay has revealed the specific steps in the crossbridge cycle affected by these ions. In addition to their direct effects, these ions also indirectly affect myosin by decreasing the sensitivity of the myofilaments to calcium, primarily by altering the ability of the muscle regulatory proteins, troponin and tropomyosin, to govern myosin binding to actin. This effect seems to be partially due to fatigue-dependent alterations in the structure and function of specific subunits of troponin. Parallel efforts to understand the molecular basis of muscle contraction are providing new technological approaches that will allow us to gain unprecedented molecular detail of the fatigue process. This will be crucial to fully understand this ubiquitous phenomenon and develop appropriately targeted therapies to attenuate the debilitating effects of fatigue in clinical populations

Nitric oxide regulates skeletal muscle fatigue, fiber type, microtubule organization, and mitochondrial ATP synthesis efficiency through cGMP-dependent mechanisms

Aim: Skeletal muscle nitric oxide–cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSμ and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. Results: GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSμ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1−/− muscle. Functional analyses of GC1−/− muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA–IIX fiber balance. Force deficits in GC1−/− muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. Innovation: GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. Conclusions: These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency

Muscle fiber typology substantially influences time to recover from high-intensity exercise

Human fast-twitch muscle fi- bers generate high power in a short amount of time but are easily fatigued, whereas slow-twitch fibers are more fatigue resistant. The transfer of this knowledge to coaching is hampered by the invasive nature of the current evaluation of muscle typology by biopsies. Therefore, a noninvasive method was developed to estimate muscle typology through proton magnetic resonance spectroscopy in the gastrocnemius. The aim of this study was to investigate whether male subjects with an a priori-determined fast typology (FT) are character- ized by a more pronounced Wingate exercise-induced fatigue and delayed recovery compared with subjects with a slow typology (ST). Ten subjects with an estimated higher percentage of fast-twitch fibers and 10 subjects with an estimated higher percentage of slow-twitch fibers underwent the test protocol, consisting of three 30-s all-out Wingate tests. Recovery of knee extension torque was evaluated by maximal voluntary contraction combined with electrical stimulation up to 5 h after the Wingate tests. Although both groups delivered the same mean power across all Wingates, the power drop was higher in the FT group (—61%) compared with the ST group (—41%). The torque at maximal voluntary contraction had fully recovered in the ST group after 20 min, whereas the FT group had not yet recovered 5 h into recovery. This noninvasive estimation of muscle typology can predict the extent of fatigue and time to recover following repeated all-out exercise and may have applications as a tool to individualize training and recovery cycles. NEW & NOTEWORTHY A one-fits-all training regime is present in most sports, though the same training implies different stimuli in athletes with a distinct muscle typology. Individualization of training based on this muscle typology might be important to optimize per- formance and to lower the risk for accumulated fatigue and potentially injury. When conducting research, one should keep in mind that the muscle typology of participants influences the severity of fatigue and might therefore impact the results

Effects of Low Cell pH and Elevated Inorganic Phosphate on the pCa-Force Relationship in Single Muscle Fibers at Near-Physiological Temperatures

Intense muscle contraction induces high rates of ATP hydrolysis with resulting increases in Pi, H+, and ADP, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.2 and collective effects with 30 mM Pi on the pCa-force relationship were assessed in skinned fast and slow rat skeletal muscle fibers at 15 and 30°C. At 30°C, pH 6.2 + 30 mM Pi significantly depressed peak force in all fiber types, with the greatest effect in type IIx fibers. Across fiber types, Ca2+ sensitivity was depressed by low pH and low pH + high Pi, with the greater effect at 30°C. For type IIx fibers at 30°C, half-maximal activation (pCa50) was 5.36 at pH 6.2 (no added Pi) and 4.98 at pH 6.2 + 30 mM Pi compared with 6.58 in the control condition (pH 7, no added Pi). At 30°C, n2, reflective of thick filament cooperativity, was unchanged by low cell pH but was depressed from 5.02 to 2.46 in type IIx fibers with pH 6.2 + 30 mM Pi. With acidosis, activation thresholds of all fiber types required higher free Ca2+ at 15 and 30°C. With the exception of type IIx fibers, the Ca2+ required to reach activation threshold increased further with added Pi. In conclusion, it is clear that fatigue-inducing effects of low cell pH and elevated Pi at near-physiological temperatures are substantial