Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models.

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progressive degeneration of muscle fibers, resulting in inflammation and fibrosis that ultimately affect the overall muscle biomechanics. At the opposite end of the spectrum of muscle diseases, age-related sarcopenia is a common condition that affects an increasing proportion of the elderly. Although characterized by different pathological mechanisms, DMD and sarcopenia share the development of progressive muscle weakness and tissue inflammation. Here, the therapeutic effects of Cyclo Histidine-Proline (CHP) against DMD and sarcopenia are evaluated. In the mdx mouse model of DMD, it is shown that CHP restored muscle contractility and force production, accompanied by the reduction of fibrosis and inflammation in skeletal muscle. CHP furthermore prevented the development of cardiomyopathy and fibrosis in the diaphragm, the two leading causes of death for DMD patients. CHP also attenuated muscle atrophy and functional deterioration in a mouse model of age-related sarcopenia. These findings from two different models of muscle dysfunction hence warrant further investigation into the effects of CHP on muscle pathologies in animal models and eventually in patients.

Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

The first and second phases of the muscle compound action potential in the thumb are differently affected by electrical stimulation trains.

Sarcolemmal membrane excitability is often evaluated by considering the peak-to-peak amplitude of the compound muscle action potential (M wave). However, the first and second M-wave phases represent distinct properties of the muscle action potential, which are differentially affected by sarcolemma properties and other factors such as muscle architecture. Contrasting with previous studies in which voluntary contractions have been used to induce muscle fatigue, we used repeated electrically induced tetanic contractions of the adductor pollicis muscle and assessed the kinetics of M-wave properties during the course of the contractions. Eighteen participants (24 ± 6 yr; means ± SD) underwent 30 electrically evoked tetanic contractions delivered at 30 Hz, each lasting 3 s with 1 s intervals. We recorded the amplitudes of the first and second M-wave phases for each stimulation. During the initial stimulation train, the first and second M-wave phases exhibited distinct kinetics. The first phase amplitude showed a rapid decrease to reach ∼59% of its initial value (P < 0.001), whereas the second phase amplitude displayed an initial transient increase of ∼19% (P = 0.007). Within subsequent trains, both the first and second phase amplitudes consistently decreased as fatigue developed with a reduction during the last train reaching ∼47% of its initial value (P < 0.001). Analyzing the first M wave of each stimulation train unveiled different kinetics for the first and second phases during the initial trains, but these distinctions disappeared as fatigue progressed. These findings underscore the interplay of factors affecting the M wave and emphasize the significance of separately scrutinizing its first and second phases when assessing membrane excitability adjustments during muscle contractions.NEW & NOTEWORTHY Our understanding of how the first and second phases of the compound muscle action potential (M wave) behave during fatigue remains incomplete. Using electrically evoked repeated tetanic contractions of the adductor pollicis, we showed that the first and second phases of the M wave followed distinct kinetics only during the early stages of fatigue development. This suggests that the factors affecting the M-wave first and second phases may change as fatigue develops.

Functional hypoxia reduces mitochondrial calcium uptake.

Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in oxygen levels. How changes in respiration under functional hypoxia (i.e., when intracellular O2 levels limit mitochondrial respiration) are relayed by the electron transfer system to impact mitochondrial adaption and remodeling after hypoxic exposure remains poorly defined. This is largely due to challenges integrating findings under controlled and defined O2 levels in studies connecting functions of isolated mitochondria to humans during physical exercise. Here we present experiments under conditions of hypoxia in isolated mitochondria, myotubes and exercising humans. Performing steady-state respirometry with isolated mitochondria we found that oxygen limitation of respiration reduced electron flow and oxidative phosphorylation, lowered the mitochondrial membrane potential difference, and decreased mitochondrial calcium influx. Similarly, in myotubes under functional hypoxia mitochondrial calcium uptake decreased in response to sarcoplasmic reticulum calcium release for contraction. In both myotubes and human skeletal muscle this blunted mitochondrial adaptive responses and remodeling upon contractions. Our results suggest that by regulating calcium uptake the mitochondrial electron transfer system is a hub for coordinating cellular adaption under functional hypoxia.

Ryanodine receptor type 1 content decrease-induced endoplasmic reticulum stress is a hallmark of myopathies.

BACKGROUND: Decreased ryanodine receptor type 1 (RyR1) protein levels are a well-described feature of recessive RYR1-related myopathies. The aim of the present study was twofold: (1) to determine whether RyR1 content is also decreased in other myopathies and (2) to investigate the mechanisms by which decreased RyR1 protein triggers muscular disorders. METHODS: We used publicly available datasets, muscles from human inflammatory and mitochondrial myopathies, an inducible muscle-specific RYR1 recessive mouse model and RyR1 knockdown in C2C12 muscle cells to measure RyR1 content and endoplasmic reticulum (ER) stress markers. Proteomics, lipidomics, molecular biology and transmission electron microscopy approaches were used to decipher the alterations associated with the reduction of RyR1 protein levels. RESULTS: RYR1 transcripts were reduced in muscle samples of patients suffering from necrotizing myopathy (P = 0.026), inclusion body myopathy (P = 0.003), polymyositis (P < 0.001) and juvenile dermatomyositis (P < 0.001) and in muscle samples of myotonic dystrophy type 2 (P < 0.001), presymptomatic (P < 0.001) and symptomatic (P < 0.001) Duchenne muscular dystrophy, Becker muscular dystrophy (P = 0.004) and limb-girdle muscular dystrophy type 2A (P = 0.004). RyR1 protein content was also significantly decreased in inflammatory myopathy (-75%, P < 0.001) and mitochondrial myopathy (-71%, P < 0.001) muscles. Proteomics data showed that depletion of RyR1 protein in C2C12 myoblasts leads to myotubes recapitulating the common molecular alterations observed in myopathies. Mechanistically, RyR1 protein depletion reduces ER-mitochondria contact length (-26%, P < 0.001), Ca2+ transfer to mitochondria (-48%, P = 0.002) and the mitophagy gene Parkinson protein 2 transcripts (P = 0.037) and induces mitochondrial accumulation (+99%, P = 0.005) and dysfunction (P < 0.001). This was associated to the accumulation of deleterious sphingolipid species. Our data showed increased levels of the ER stress marker chaperone-binding protein/glucose regulated protein 78, GRP78-Bip, in RyR1 knockdown myotubes (+45%, P = 0.046), in mouse RyR1 recessive muscles (+58%, P = 0.001) and in human inflammatory (+96%, P = 0.006) and mitochondrial (+64%, P = 0.049) myopathy muscles. This was accompanied by increased protein levels of the pro-apoptotic protein CCAAT-enhancer-binding protein homologous protein, CHOP-DDIT3, in RyR1 knockdown myotubes (+27%, P < 0.001), mouse RyR1 recessive muscles (+63%, P = 0.009), human inflammatory (+50%, P = 0.038) and mitochondrial (+51%, P = 0.035) myopathy muscles. In publicly available datasets, the decrease in RYR1 content in myopathies was also associated to increased ER stress markers and RYR1 transcript levels are inversely correlated with ER stress markers in the control population. CONCLUSIONS: Decreased RyR1 is commonly observed in myopathies and associated to ER stress in vitro, in mouse muscle and in human myopathy muscles, suggesting a potent role of RyR1 depletion-induced ER stress in the pathogenesis of myopathies.

M-wave changes caused by brief voluntary and stimulated isometric contractions.

INTRODUCTION: Under isometric conditions, the increase in muscle force is accompanied by a reduction in the fibers' length. The effects of muscle shortening on the compound muscle action potential (M wave) have so far been investigated only by computer simulation. This study was undertaken to assess experimentally the M-wave changes caused by brief voluntary and stimulated isometric contractions. METHODS: Two different methods of inducing muscle shortening under isometric condition were adopted: (1) applying a brief (1 s) tetanic contraction and (2) performing brief voluntary contractions of different intensities. In both methods, supramaximal stimulation was applied to the brachial plexus and femoral nerves to evoke M waves. In the first method, electrical stimulation (20 Hz) was delivered with the muscle at rest, whereas in the second, stimulation was applied while participants performed 5-s stepwise isometric contractions at 10, 20, 30, 40, 50, 60, 70, and 100% MVC. The amplitude and duration of the first and second M-wave phases were computed. RESULTS: The main findings were: (1) on application of tetanic stimulation, the amplitude of the M-wave first phase decreased (~ 10%, P < 0.05), that of the second phase increased (~ 50%, P < 0.05), and the M-wave duration decreased (~ 20%, P < 0.05) across the first five M waves of the tetanic train and then plateaued for the subsequent responses; (2) when superimposing a single electrical stimulus on muscle contractions of increasing forces, the amplitude of the M-wave first phase decreased (~ 20%, P < 0.05), that of the second phase increased (~ 30%, P < 0.05), and M-wave duration decreased (~ 30%, P < 0.05) as force was raised from 0 to 60-70% MVC force. CONCLUSIONS: The present results will help to identify the adjustments in the M-wave profile caused by muscle shortening and also contribute to differentiate these adjustments from those caused by muscle fatigue and/or changes in Na+-K+ pump activity.

Individualized Mental Fatigue Does Not Impact Neuromuscular Function and Exercise Performance.

INTRODUCTION: Recent studies have questioned previous empirical evidence that mental fatigue negatively impacts physical performance. The purpose of this study was to investigate the critical role of individual differences in mental fatigue susceptibility by analyzing the neurophysiological and physical responses to an individualized mental fatigue task. METHODS: In a preregistered ( https://osf.io/xc8nr/ ), randomized, within-participant design experiment, 22 recreational athletes completed a time to failure test at 80% of their peak power output under mental fatigue (individual mental effort) or control (low mental effort). Before and after the cognitive tasks, subjective feeling of mental fatigue, neuromuscular function of the knee extensors, and corticospinal excitability were measured. Sequential Bayesian analysis until it reached strong evidence in favor of the alternative hypothesis (BF 10 > 6) or the null hypothesis (BF 10 < 1/6) were conducted. RESULTS: The individualized mental effort task resulted in a higher subjective feeling of mental fatigue in the mental fatigue condition (0.50 (95% confidence interval (CI), 0.39-0.62)) arbitrary units compared with control (0.19 (95% CI, 0.06-0.339)) arbitrary unit. However, exercise performance was similar in both conditions (control: 410 (95% CI, 357-463) s vs mental fatigue: 422 (95% CI, 367-477) s, BF 10 = 0.15). Likewise, mental fatigue did not impair knee extensor maximal force-generating capacity (BF 10 = 0.928) and did not change the extent of fatigability or its origin after the cycling exercise. CONCLUSIONS: There is no evidence that mental fatigue adversely affects neuromuscular function or physical exercise; even if mental fatigue is individualized, computerized tasks seem not to affect physical performance.

Acute Effects of Neuromuscular Electrical Stimulation on Contralateral Plantar Flexor Neuromuscular Function.

Contralateral facilitation, i.e., the increase in contralateral maximal voluntary strength that is observed when neuromuscular electrical stimulation (NMES) is applied to the ipsilateral homonymous muscle, has previously been reported for the knee extensors but the neurophysiological mechanisms remain to be investigated. The aim of this study was to compare plantar flexor contralateral facilitation between a submaximal voluntary contraction (~10% MVC torque) and two evoked contractions (conventional and wide-pulse high-frequency NMES) of the ipsilateral plantar flexors, with respect to a resting condition. Contralateral MVC torque and voluntary activation level were measured in 22 healthy participants while the ipsilateral plantar flexors were at rest, voluntarily contracted or stimulated for 15 s. Additional neurophysiological parameters (soleus H-reflex and V-wave amplitude and tibialis anterior coactivation level) were quantified in a subgroup of 12 participants. Conventional and wide-pulse high-frequency NMES of the ipsilateral plantar flexors did not induce any contralateral facilitation of maximal voluntary strength and activation with respect to the resting condition. Similarly, no alteration of neurophysiological parameters was observed in the different conditions. This absence of contralateral facilitation contrasts with some results previously obtained on the knee extensors but is consistent with the absence of neurophysiological changes on the contralateral soleus.

Inhibition of sphingolipid de novo synthesis counteracts muscular dystrophy.

Duchenne muscular dystrophy (DMD), the most common muscular dystrophy, is a severe muscle disorder, causing muscle weakness, loss of independence, and premature death. Here, we establish the link between sphingolipids and muscular dystrophy. Transcripts of sphingolipid de novo biosynthesis pathway are up-regulated in skeletal muscle of patients with DMD and other muscular dystrophies, which is accompanied by accumulation of metabolites of the sphingolipid pathway in muscle and plasma. Pharmacological inhibition of sphingolipid synthesis by myriocin in the mdx mouse model of DMD ameliorated the loss in muscle function while reducing inflammation, improving Ca2+ homeostasis, preventing fibrosis of the skeletal muscle, heart, and diaphragm, and restoring the balance between M1 and M2 macrophages. Myriocin alleviated the DMD phenotype more than glucocorticoids. Our study identifies inhibition of sphingolipid synthesis, targeting multiple pathogenetic pathways simultaneously, as a strong candidate for treatment of muscular dystrophies.

Sphingolipids accumulate in aged muscle, and their reduction counteracts sarcopenia.

Age-related muscle dysfunction and sarcopenia are major causes of physical incapacitation in older adults and currently lack viable treatment strategies. Here we find that sphingolipids accumulate in mouse skeletal muscle upon aging and that both genetic and pharmacological inhibition of sphingolipid synthesis prevent age-related decline in muscle mass while enhancing strength and exercise capacity. Inhibition of sphingolipid synthesis confers increased myogenic potential and promotes protein synthesis. Within the sphingolipid pathway, we show that accumulation of dihydroceramides is the culprit disturbing myofibrillar homeostasis. The relevance of sphingolipid pathways in human aging is demonstrated in two cohorts, the UK Biobank and Helsinki Birth Cohort Study in which gene expression-reducing variants of SPTLC1 and DEGS1 are associated with improved and reduced fitness of older individuals, respectively. These findings identify sphingolipid synthesis inhibition as an attractive therapeutic strategy for age-related sarcopenia and co-occurring pathologies.

Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity.

Sustained ryanodine receptor (RyR) Ca2+ leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training (MICT), triggers RyR1 protein oxidation and nitrosylation leading to calstabin1 dissociation in healthy human muscle and in in vitro SIT models (simulated SIT or S-SIT). This is accompanied by decreased sarcoplasmic reticulum Ca2+ content, increased levels of mitochondrial oxidative phosphorylation proteins, supercomplex formation and enhanced NADH-linked mitochondrial respiratory capacity. Mechanistically, (S-)SIT increases mitochondrial Ca2+ uptake in mouse myotubes and muscle fibres, and decreases pyruvate dehydrogenase phosphorylation in human muscle and mouse myotubes. Countering Ca2+ leak or preventing mitochondrial Ca2+ uptake blunts S-SIT-induced adaptations, a result supported by proteomic analyses. Here we show that triggering acute transient Ca2+ leak through RyR1 in healthy muscle may contribute to the multiple health promoting benefits of exercise.

Sarcolemmal Excitability, M-Wave Changes, and Conduction Velocity During a Sustained Low-Force Contraction.

This study was undertaken to investigate whether sarcolemmal excitability is impaired during a sustained low-force contraction [10% maximal voluntary contraction (MVC)] by assessing muscle conduction velocity and also by analyzing separately the first and second phases of the muscle compound action potential (M wave). Twenty-one participants sustained an isometric knee extension of 10% MVC for 3min. M waves were evoked by supramaximal single shocks to the femoral nerve given at 10-s intervals. The amplitude, duration, and area of the first and second M-wave phases were computed. Muscle fiber conduction velocity, voluntary surface electromyographic (EMG), perceived effort, MVC force, peak twitch force, and temperature were also recorded. The main findings were: (1) During the sustained contraction, conduction velocity remained unchanged. (2) The amplitude of the M-wave first phase decreased for the first ~30s (-7%, p<0.05) and stabilized thereafter, whereas the second phase amplitude increased for the initial ~30s (+7%, p<0.05), before stabilizing. (3) Both duration and area decreased steeply during the first ~30s, and then more gradually for the rest of the contraction. (4) During the sustained contraction, perceived effort increased fivefold, whereas knee extension EMG increased by ~10%. (5) Maximal voluntary force and peak twitch force decreased (respectively, -9% and -10%, p<0.05) after the low-force contraction. Collectively, the present results indicate that sarcolemmal excitability is well preserved during a sustained 10% MVC task. A depression of the M-wave first phase during a low-force contraction can occur even in the absence of changes in membrane excitability. The development of fatigue during a low-force contraction can occur without alteration of membrane excitability.

The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection.

Regular exercise is associated with pronounced health benefits. The molecular processes involved in physiological adaptations to exercise are best understood in skeletal muscle. Enhanced mitochondrial functions in muscle are central to exercise-induced adaptations. However, regular exercise also benefits the brain and is a major protective factor against neurodegenerative diseases, such as the most common age-related form of dementia, Alzheimer's disease, or the most common neurodegenerative motor disorder, Parkinson's disease. While there is evidence that exercise induces signalling from skeletal muscle to the brain, the mechanistic understanding of the crosstalk along the muscle-brain axis is incompletely understood. Mitochondria in both organs, however, seem to be central players. Here, we provide an overview on the central role of mitochondria in exercise-induced communication routes from muscle to the brain. These routes include circulating factors, such as myokines, the release of which often depends on mitochondria, and possibly direct mitochondrial transfer. On this basis, we examine the reported effects of different modes of exercise on mitochondrial features and highlight their expected benefits with regard to neurodegeneration prevention or mitigation. In addition, knowledge gaps in our current understanding related to the muscle-brain axis in neurodegenerative diseases are outlined.

Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, and despite advances in genetic and pharmacological disease-modifying treatments, its management remains a major challenge. Mitochondrial dysfunction contributes to DMD, yet the mechanisms by which this occurs remain elusive. Our data in experimental models and patients with DMD show that reduced expression of genes involved in mitochondrial autophagy, or mitophagy, contributes to mitochondrial dysfunction. Mitophagy markers were reduced in skeletal muscle and in muscle stem cells (MuSCs) of a mouse model of DMD. Administration of the mitophagy activator urolithin A (UA) rescued mitophagy in DMD worms and mice and in primary myoblasts from patients with DMD, increased skeletal muscle respiratory capacity, and improved MuSCs' regenerative ability, resulting in the recovery of muscle function and increased survival in DMD mouse models. These data indicate that restoration of mitophagy alleviates symptoms of DMD and suggest that UA may have potential therapeutic applications for muscular dystrophies.

Modulation of torque evoked by wide-pulse, high-frequency neuromuscular electrical stimulation and the potential implications for rehabilitation and training.

The effectiveness of neuromuscular electrical stimulation (NMES) for rehabilitation is proportional to the evoked torque. The progressive increase in torque (extra torque) that may develop in response to low intensity wide-pulse high-frequency (WPHF) NMES holds great promise for rehabilitation as it overcomes the main limitation of NMES, namely discomfort. WPHF NMES extra torque is thought to result from reflexively recruited motor units at the spinal level. However, whether WPHF NMES evoked force can be modulated is unknown. Therefore, we examined the effect of two interventions known to change the state of spinal circuitry in opposite ways on evoked torque and motor unit recruitment by WPHF NMES. The interventions were high-frequency transcutaneous electrical nerve stimulation (TENS) and anodal transcutaneous spinal direct current stimulation (tsDCS). We show that TENS performed before a bout of WPHF NMES results in lower evoked torque (median change in torque time-integral: - 56%) indicating that WPHF NMES-evoked torque might be modulated. In contrast, the anodal tsDCS protocol used had no effect on any measured parameter. Our results demonstrate that WPHF NMES extra torque can be modulated and although the TENS intervention blunted extra torque production, the finding that central contribution to WPHF NMES-evoked torques can be modulated opens new avenues for designing interventions to enhance WPHF NMES.

Key Nutritional Considerations for Youth Winter Sports Athletes to Optimize Growth, Maturation and Sporting Development.

Despite a wealth of sport nutrition guidelines for adult athletes, there are currently no nutrition guidelines for youth winter sports athletes. Whilst it may be pragmatic to apply nutrition guidelines for adult athletes to youth winter sports athletes, it is inappropriate. Due to a paucity of research on youth athletes, it is impossible to provide evidence-based guidelines for this population, so careful extrapolation from the theoretical and practical considerations that apply to other athletic groups is necessary. Youth winter sport athletes undergo rapid biological growth and maturation which influences their nutritional requirements. A varied and balanced diet that ensures sufficient energy availability for optimal growth and maturation as well as sporting performance is the cornerstone of youth athlete nutrition and should also allow for youth athletes to meet their micronutrient requirements. In some cases, micronutrient status (e.g., vitamin D and iron) should be monitored and optimized if appropriate by a medical professional. Dietary supplement use is prevalent amongst youth athletes, however is often unnecessary. Education of youth athletes, their parents and coaches on best nutritional practices as well as the risks associated with dietary supplements is vital for their long-term athletic development. Further research in youth winter sports athletes across different stages of growth and maturation competing in a variety of sports is urgently required in order to inform nutritional guidelines for this population.

Muscle fibre conduction velocity varies in opposite directions after short- vs. long-duration muscle contractions.

INTRODUCTION: The effects of muscle contractions on muscle fibre conduction velocity have normally been investigated for contractions of a given duration and intensity, with most studies being focused on the decline on conduction velocity during/after prolonged contractions. Herein, we perform a systematic analysis of the changes in conduction velocity after voluntary contractions of different durations and intensities. METHODS: Conduction velocity was estimated in the vastus lateralis before and after knee extensor isometric maximal voluntary contractions (MVCs) of 1, 3, 6, 10, 30 and 60 s, and after brief (3 s) contractions at 10, 30, 50, 70, and 90% of MVC force. Measurements were made during the 10-min period following each contraction. RESULTS: (1) Conduction velocity was increased immediately after (1 s) the MVCs of brief (≤ 10 s) duration (12 ± 2%, P < 0.05), and then returned rapidly (within 15 s) to control levels; (2) the extent of the increase in conduction velocity was similar after the 3-s, 6-s, and 10-s MVCs (P > 0.05); (3) the magnitude of the increase in conduction velocity after a brief contraction augmented with the intensity of the contraction (increases of 4.6, 7.7, 11.4, 14.8, and 15.2% for contractions at 10, 30, 50, 70, and 90% of MVC force, respectively); (4) conduction velocity was not decreased immediately after the 30-s MVC (P > 0.05); and (5) conduction velocity did not reach its minimum 1 s after the long (≥ 30 s) MVCs. CONCLUSIONS: Brief (≤ 10 s) muscle contractions induce a short-term increase in conduction velocity, lasting 15 s, while long (≥ 30 s) contractions produce a long-term decrease in conduction velocity, lasting more than 2 min.

The M waves of the biceps brachii have a stationary (shoulder-like) component in the first phase: implications and recommendations for M-wave analysis.

OBJECTIVE: We recently documented that compound muscle action potentials (M waves) recorded over the 'pennate' vastus lateralis showed a sharp deflection (named as a shoulder) in the first phase. Here, we investigated whether such a shoulder was also present in M waves evoked in a muscle with different architecture, such as the biceps brachii, with the purpose of elucidating the electrical origin of such afeature. APPROACH: M waves evoked by maximal single shocks to the brachial plexus were recorded in monopolar and bipolar configurations from 72 individuals using large (10 mm diameter) electrodes and from eight individuals using small (1 mm diameter) electrodes arranged in a linear array. The changes in M-wave features at different locations along the muscle fiber direction were examined. MAIN RESULTS: The shoulder was recognizable in most (87%) monopolar M waves, whereas it was rarely observed (6%) in bipolar derivations. Recordings made along the fiber direction showed that the shoulder was a stationary (non-propagating) feature, with short duration (spiky), which had positive polarity at all locations along the fibers. The latency of the shoulder (9.5 ± 0.5 ms) was significantly shorter than the estimated time taken for the action potentials to reach the biceps tendon (12.8 ms). SIGNIFICANCE: The shoulder must be generated by a dipole source, i.e. a source created at a fixed anatomical position, although the exact origin of this dipole is uncertain. Our results suggest that the shoulder may not be due to the end-of-fiber signals formed at the biceps brachii tendon. The shoulder is not related to any specific arrangement of muscle fibers, as it has been observed in both pennate and fusiform muscles. Being a stationary (non-propagating) component, the shoulder is not reliable for studying changes in sarcolemmal excitability, and thus should be excluded from the M-wave analysis.