Muscle Physiology

Obesity  and  accompanying  type  2  diabetes  are  among  major  and  increasing  world-wide problems that occur fundamentally due to excessive energy intake during its expenditure.Endotherms continuouslyconsume a certain amount of energy to maintain core body temperaturevia thermogenic processes, mainly in brown adipose tissue and skeletal muscle. Skeletal muscle glu-cose utilization and heat production are significant and directly linked to body glucose homeostasisat rest, and especially during physical activity. However, this glucose balance is impaired in diabeticand obese states in humans and mice, and manifests as glucose resistance and altered muscle cellmetabolism. Uncoupling proteins have a significant role in converting electrochemical energy intothermal energy without ATP generation. Different homologs of uncoupling proteins were identified,and their roles were linked to antioxidative activity and boosting glucose and lipid metabolism.From this perspective, uncoupling proteins were studied in correlation to the pathogenesis of dia-betes and obesity and their possible treatments. Mice were extensively used as model organisms tostudy the physiology and pathophysiology of energy homeostasis. However, we should be aware ofinterstrain differences in mice models of obesity regarding thermogenesis and insulin resistance inskeletal muscles. Therefore, in this review, we gathered up-to-date knowledge on skeletal muscleuncoupling proteins and their effect on insulin sensitivity in mouse models of obesity and diabetes.

This study compared the rate of muscle temperature (T m) increase during acute whole-body vibration (WBV), to that of stationary cycling and passive warm-up. Additionally we wanted to determine if the purported increase in counter-movement jump and peak power cycling from acute WBV could be explained by changes in muscle temperature. Eight active participants volunteered for the study, which involved a rest period of 30 min to collect baseline measures of muscle, core, skin temperature, heart rate (HR), and thermal leg sensation (TLS), which was followed by three vertical jumps and 5 s maximal cycle performance test. A second rest period of 40 min was enforced followed by the intervention and performance tests. The change in T m elicited during cycling was matched in the hot bath and WBV interventions. Therefore cycling was performed first, proceeded by, in a random order of hot bath and acute WBV. The rate of T m was significantly greater (P < 0.001) during acute WBV (0.30°C min−1) compared to cycle (0.15°C min−1) and hot bath (0.09°C min−1) however there was no difference between the cycle and hot bath, and the metabolic rate was the same in cycling and WBV (19 mL kg−1 min−1). All three interventions showed a significant (P < 0.001) increase in countermovement jump peak power and height. For the 5 s maximal cycle test (MIC) there were no significant differences in peak power between the three interventions. In conclusion, acute WBV elevates T m more quickly than traditional forms of cycling and passive warm-up. Given that all three warm-up methods yielded the same increase in peak power output, we propose that the main effect is caused by the increase in T m.

Maganaris, Constantinos N., Vasilios Baltzopoulos, D. Ball, and Anthony J. Sargeant. In vivo specific tension of human skeletal muscle. J Appl Physiol 90: [865][866][867][868][869][870][871][872] 2001.-In this study, we estimated the specific tensions of soleus (Sol) and tibialis anterior (TA) muscles in six men. Joint moments were measured during maximum voluntary contraction (MVC) and during electrical stimulation. Moment arm lengths and muscle volumes were measured using magnetic resonance imaging, and pennation angles and fascicular lengths were measured using ultrasonography. Tendon and muscle forces were modeled. Two approaches were followed to estimate specific tension. First, muscle moments during electrical stimulation and moment arm lengths, fascicular lengths, and pennation angles during MVC were used (data set A). Then, MVC moments, moment arm lengths at rest, and cadaveric fascicular lengths and pennation angles were used (data set B). The use of data set B yielded the unrealistic specific tension estimates of 104 kN/m 2 in Sol and 658 kN/m 2 in TA. The use of data set A, however, yielded values of 150 and 155 kN/m 2 in Sol and TA, respectively, which agree with in vitro results from fiber type I-predominant muscles. In fact, both Sol and TA are such muscles. Our study demonstrates the feasibility of accurate in vivo estimates of human muscle intrinsic strength.

Reduced signaling through the C. elegans insulin/insulinlike growth factor-1-like tyrosine kinase receptor daf-2 and dietary restriction via bacterial dilution are two wellcharacterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LC-MS/MS quantitative proteomics, we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction, as well as in the daf-2(e1370) insulin/insulin-like growth factor-1-receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that post-transcriptional regulation determines ribosome content. Proteomics also revealed the increased presence of many structural muscle cell components in long-lived worms, which appeared to result from the prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF-16, but not diet restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf-2-specific proteome changes include overexpression of aerobic metabolism enzymes and general activation of stress-responsive and immune defense systems, whereas the increased abundance of many protein subunits of the proteasome core complex is a dietaryrestriction-specific characteristic. Molecular & Cellular

The purpose of the present study was to investigate the effect of temperature on the rates of isometric force development and relaxation in electrically activated fresh and fatigued human adductor pollicis muscle. Following immersion of the lower arm for 20 min in water baths of four different temperatures, muscle temperatures were approximately 37, 31, 25 and 22 'C. Maximal isometric force was reduced by 16-8 + 1.5 % at 22 'C. The stimulation frequency-force and -rate of force development relationships were shifted to the left at lower temperatures. Q10 values for the maximal rates of force development and relaxation, and the times for 100 to 50 % and 50 to 25 % force relaxation, were about 2-0 between 37 and 25 'C and about 3-8 between 25 and 22 'C. However, the time for 50 to 25 % force relaxation had a relatively high Q1o value between 25 and 22 'C (6-9) and this parameter also appeared to be more sensitive to fatigue compared to the other indices of relaxation. Nevertheless, the effect of fatigue on all parameters decreased with cooling over the entire (37-22°C) temperature range.

Skeletal muscle fat infiltration (known as myosteatosis) is an ectopic fat depot that increases with aging and is recognized to negatively correlate with muscle mass, strength, and mobility and disrupt metabolism (insulin resistance, diabetes). An interdisciplinary workshop convened by the National Institute on Aging Division of Geriatrics and Clinical Gerontology on September 2018, discussed myosteatosis in the context of skeletal muscle function deficit (SMFD). Its purpose was to gain a better understanding of the roles of myosteatosis in aging muscles and metabolic disease, particularly its potential determinants and clinical consequences, and ways of properly assessing it. Special attention was given to functional status and standardization of measures of body composition (including the value of D 3-creatine dilution method) and imaging approaches [including ways to better use dual-energy X-ray absorptiometry (DXA) through the shape and appearance modeling] to assess lean mass, sarcopenia, and myosteatosis. The workshop convened innovative new areas of scientific relevance to light such as the effect of circadian rhythms and clock disruption in skeletal muscle structure, function, metabolism, and potential contribution to increased myosteatosis. A muscle-bone interaction perspective compared mechanisms

Assessment of mitochondrial ADP-stimulated respiratory kinetics in PmFBs (permeabilized fibre bundles) is increasingly used in clinical diagnostic and basic research settings. However, estimates of the Km for ADP vary considerably (~20-300 μM) and tend to overestimate respiration at rest. Noting that PmFBs spontaneously contract during respiration experiments, we systematically determined the impact of contraction, temperature and oxygenation on ADP-stimulated respiratory kinetics. BLEB (blebbistatin), a myosin II ATPase inhibitor, blocked contraction under all conditions and yielded high Km values for ADP of >~250 and ~80 μM in red and white rat PmFBs respectively. In the absence of BLEB, PmFBs contracted and the Km for ADP decreased ~2-10-fold in a temperature-dependent manner. PmFBs were sensitive to hyperoxia (increased Km) in the absence of BLEB (contracted) at 30 °C but not 37 °C. In PmFBs from humans, contraction elicited high sensitivity to ADP (Km<100 μM), whereas blocking contraction (+BLEB) and including a phosphocreatine/creatine ratio of 2:1 to mimic the resting energetic state yielded a Km for ADP of ~1560 μM, consistent with estimates of in vivo resting respiratory rates of <1% maximum. These results demonstrate that the sensitivity of muscle to ADP varies over a wide range in relation to contractile state and cellular energy charge, providing evidence that enzymatic coupling of energy transfer within skeletal muscle becomes more efficient in the working state.

In the context of resistance training the so-called "sticking point"  is commonly understood as the position in a lift in which a disproportionately large increase in the difficulty to continue the lift is experienced.  If the lift is taken to the point of momentary muscular failure, the sticking point is usually where the failure occurs.  Hence the sticking point is associated with an increased chance of exercise form deterioration or breakdown.  Understanding the mechanisms that lead to the occurrence of sticking points, as well as different training strategies which can be used to overcome them is important to strength practitioners (trainees and coaches alike), and instrumental for the avoidance of injury and continued progress.  In this paper we survey and consolidate the body of existing research on the topic: we discuss different definitions of the sticking point adopted in the literature and propose a more precise definition, describe different muscular and biomechanical aspects which give rise to sticking points, and review the effectiveness of different training modalities used to address them.

1. It has been established that pulmonary oxygen uptake is greater during cycle exercise in humans at high compared to low contraction frequencies. However, it is unclear whether this is due to more work being performed at the high frequencies and whether the energy turnover of the working muscles is higher. The present study tested the hypothesis that human skeletal muscle oxygen uptake and energy turnover are elevated during exercise at high compared to low contraction frequency when the total power output is the same.

An a priori model of the whole active muscle length-tension relationship was constructed utilizing only myofilament length and serial sarcomere number for rabbit tibialis anterior (TA), extensor digitorum longus (EDL), and extensor digitorum II (EDII) muscles. Passive tension was modeled with a two-element Hill-type model. Experimental length-tension relations were then measured for each of these muscles and compared to predictions. The model was able to accurately capture the active -tension characteristics of experimentally-measured data for all muscles (ICC=0.88±0.03). Despite their varied architecture, no differences in predicted versus experimental correlations were observed among muscles. In addition, the model demonstrated that excursion, quantified by full-width-at-half-maximum (FWHM) of the active length-tension relationship, scaled linearly (slope=0.68) with normalized muscle fiber length. Experimental and theoretical FWHM values agreed well with an intraclass correlation coefficient of 0.99 (p < 0.001). In contrast to active tension, the passive tension model deviated from experimentally-measured values and thus, was not an accurate predictor of passive tension (ICC=0.70±0.07). These data demonstrate that modeling muscle as a scaled sarcomere provides accurate active functional predictions for rabbit TA, EDL, and EDII muscles and call into question the need for more complex modeling assumptions often proposed.

Thermal stress is known to impair endurance capacity during moderate prolonged exercise. However, there is relatively little available information concerning the effects of thermal stress on the performance of high-intensity short-duration exercise. The present experiment examined human power output during repeated bouts of short-term maximal exercise. On two separate occasions, seven healthy males performed two 30-s bouts of sprint exercise (sprints I and II), with 4 min of passive recovery in between, on a cycle ergometer. The sprints were performed in both a normal environment [18.7 (1.5)°C, 40 (7)% relative humidity (RH; mean SD)] and a hot environment [30.1 (0.5)°C, 55 (9)% RH]. The order of exercise trials was randomised and separated by a minimum of 4 days. Mean power, peak power and decline in power output were calculated from the flywheel velocity after correction for flywheel acceleration. Peak power output was higher when exercise was performed in the heat compared to the normal environment in both sprint I [910 (172) W vs 656 (58) W; P < 0.01] and sprint II [907 (150) vs 646 (37) W; P < 0.05]. Mean power output was higher in the heat compared to the normal environment in both sprint I [634 (91) W vs 510 (59) W; P < 0.05] and sprint II [589 (70) W vs 482 (47) W; P < 0.05]. There was a faster rate of fatigue (P < 0.05) when exercise was performed in the heat compared to the normal environment. Arterialised-venous blood samples were taken for the determination of acid-base status and blood lactate and blood glucose before exercise, 2 min after sprint I, and at several time points after sprint II. Before exercise there was no difference in resting acid-base status or blood metabolites between environmental conditions. There was a decrease in blood pH, plasma bicarbonate and base excess after sprint I and after sprint II. The degree of post-exercise acidosis was similar when exercise was performed in either of the environmental conditions. The metabolic response to exercise was similar between environmental conditions; the concentration of blood lactate increased (P < 0.01) after sprint I and sprint II but there were no differences in lactate concentration when comparing the exercise bouts performed in a normal and a hot environment. These data demonstrate that when brief intense exercise is performed in the heat, peak power output increases by about 25% and mean power output increases by 15%; this was due to achieving a higher pedal cadence in the heat.

 Combined methodologies of histochemistry, immunohistochemistry, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), reverse transcriptase polymerase chain reaction (RT-PCR) and a histochemical method specific for myofibrillar ATPase (mATPase) of the type IIX myosin heavy chain (MyHC) isoform were used to study human and rat single fibres to examine the homology between type II MyHC isoform-based fibres of both species. We demonstrate that human type II fibres exhibit antigenic mATPase and 3’-untranslated region (3’-UTR) sequence determinants homologous to the IIA and IIX but not the IIB MyHC isoforms of the rat. Both immunolabelling with anti-MyHC monoclonal antibodies and the mATPase method used with frozen sections confirmed that all human type II fibres express type IIA and/or type IIX MyHC. Quantitative immunohistochemistry failed to recognize human fibres with antigenic characteristics corresponding to hybrid IIXB MyHC-based fibres. Ca2+-stimulated maximum myosin ATPase activity, determined by quantitative histochemistry, revealed that human IIX fibres (with an optical density or OD = 0.707) display enzyme activity which is comparable to that of the rat type IIX (OD = 0.687) but lower than that of the rat type IIB fibres (OD = 0.836). The results do not support the notion that MyHC IIB is expressed in human limb muscles, even in hybrid fibres. We conclude that human type II fibres have been misclassified in numerous previous publications and that this has important implications in attempts to compare the physiological characteristics of fibre types, particularly when animal models are used.

Exertional rhabdomyolysis is a complex and poorly understood entity. The inflammatory system has an important role in muscle injury and repair. Serum creatine kinase (CK) is often used as systemic biomarker representing muscle damage. Considerable variation exists in CK response between different subjects. Genetic elements may act as predisposition factors for exertional srhabdomyolysis. Based on their biological activity, we hypothesized that in healthy subjects IL6 G-174C and TNFA G-308A promoter polymorphisms would be associated with CK response to exercise. We determined serum CK activity pre- and post-maximal eccentric contractions of the elbow flexor muscles. IL6 G-174C and TNFA G-308A genotypes were analyzed for possible relationship with changes in serum CK activity. IL6 G-174C genotype was associated with CK activity in a Dose-Dependent fashion. Subjects with one or more of the -174C allele had a greater increase and higher peak CK values than subjects homozygous for the G allele (mean ± SE U/L: GG, 2,604 ± 821; GC, 7,592 ± 1,111; CC, 8,403 ± 3,849, ANOVA P = 0.0003 for GG + GC genotypes versus CC genotype, P = 0.0005 for linear trend). IL6-174CC genotype was associated with a greater than threefold increased risk of massive CK response (adjusted odds ratio 3.29, 95% confidence interval 1.27–7.85, P = 0.009). A milder association (P = 0.06) was noted between TNFA G-308A genotype and CK activity. In conclusion, we found a strong association of the IL6 G-174C genotype with systemic CK response to strenuous exercise. Data suggest that homozygosity for the IL6-174C allele is a clinically important risk factor for exercise-induced muscle injury, further supporting the central role of cytokines in the reactive inflammatory process of muscle damage and repair.

This collection of articles forms the basis of a symposium entitled Muscle-energetic and Cardiopulmonary Determinants of Exercise Tolerance in Humans, which took place at the Physiological Society's meeting at University College London in July 2006. Recognizing that reduced exercise tolerance is a cardinal feature of ageing and of many cardiorespiratory and metabolic disease states, the purpose of this symposium was to critically address putative mechanisms that might contribute to fatigue during whole-body exercise.

Rat medial gastrocnemius (GM) muscle is a compartmentalized muscle. The functional properties and fibre type composition of the most proximal and most distal compartment were studied in in situ preparations. The proximal compartment contained predominantly fast twitch oxidative fibres. The distal compartment was mainly composed of fast twitch glycolytic fibres. With the use of two small electrodes placed around the primary nerve branches, both compartments could be separately stimulated within the same muscle. The length-force relationship was less broad and maximal twitch and tetanic forces were obtained at lower muscle lengths for the proximal compartment. The differences (mm) were 0.9 ± 0.2 and 1.2 ± 0.2 for maximal twitch and tetanic force (120 Hz) production, respectively (P < 0.001). The shortening velocity for maximal power production was lower (P < 0.001) for the proximal compartment (proximal: 57.1 ± 2.7 mm s-1, distal: 73.1 ± 3.0 mm s-1). During a standard fatigue test the fatiguability was significantly lower for the proximal compared with the distal fibres. Our findings suggest that the proximal compartment is likely to be activated in vivo during activities requiring relatively low power outputs for longer time periods. In contrast the distal compartment is probably recruited only during high power demanding short lasting activities. The presented model makes it possible to study fatigue related changes in power production of the ‘red’ and ‘white’ areas of the GM separately in a way that is probably meaningful with respect to in vivo function.

Complex interactions between the nervous, muscular, and
skeletal systems produce the wide variety of movements
available for human task execution. Each of these systems
is often studied in isolation, but movement scientists and
clinicians are forced to integrate the entire neuromusculoskeletal
system to understand functional limitations and prescribe viable
treatments. Although this approach is appropriate for clinical decision making, the details of each system are often overlooked, perhaps at the expense of accurate and/or innovative treatment approaches. The purpose of this paper was to describe the fundamental organization and physiology of the muscles controlling hip movement.

Cerebral palsy (CP) of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU) from CP patients (n = 29) and healthy controls (n = 10). The sarcomere slack length (mean 2.5 mm, SEM 0.05) and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 mm 2 , SEM 190) in spastic muscle than in controls (2572 mm 2 , SEM 322). However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold), i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23) did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients. Citation: de Bruin M, Smeulders MJ, Kreulen M, Huijing PA, Jaspers RT (2014) Intramuscular Connective Tissue Differences in Spastic and Control Muscle: A Mechanical and Histological Study. PLoS ONE 9(6): e101038.

Background: Skeletal muscle injury activates satellite cells to initiate processes of proliferation, differentiation, and hypertrophy in order to regenerate muscle fibers. The number of microRNAs and their target genes are engaged in satellite cell activation. β-Hydroxy-β-methylbutyrate (HMB) is known to prevent exercise-induced muscle damage. The purpose of this study was to evaluate the effect of HMB on miRNA and relevant target gene expression in differentiating equine satellite cells exposed to H 2 O 2. We hypothesized that HMB may regulate satellite cell activity, proliferation, and differentiation, hence attenuate the pathological processes induced during an in vitro model of H 2 O 2-related injury by changing the expression of miRNAs. Methods: Equine satellite cells (ESC) were isolated from the samples of skeletal muscle collected from young horses. ESC were treated with HMB (24 h) and then exposed to H 2 O 2 (1 h). For the microRNA and gene expression assessment microarrays, technique was used. Identified miRNAs and genes were validated using real-time qPCR. Cell viability, oxidative stress, and cell damage were measured using colorimetric method and flow cytometry.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM) components are augmented in skeletal muscles of symptomatic hSOD1 G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα), Tcf4 and α-smooth muscle actin (α-SMA) levels are augmented in the skeletal muscle of symptomatic hSOD1 G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs), which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1 G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1 G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF) signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases.

Lopata RG, van Dijk JP, Pillen S, Nillesen MM, Maas H, Thijssen JM, Stegeman DF, de Korte CL. Dynamic imaging of skeletal muscle contraction in three orthogonal directions. In this study, a multidimensional strain estimation method using biplane ultrasound is presented to assess local relative deformation (i.e., local strain) in three orthogonal directions in skeletal muscles during induced and voluntary contractions. The method was tested in the musculus biceps brachii of five healthy subjects for three different types of muscle contraction: 1) excitation of the muscle with a single electrical pulse via the musculocutaneous nerve, resulting in a so-called "twitch" contraction; 2) a train of five pulses at 10 Hz and 20 Hz, respectively, to obtain a submaximum tetanic contraction; and 3) voluntary contractions at 30, 60, and 100% of maximum contraction force. Results show that biplane ultrasound strain imaging is feasible. The method yielded adequate performance using the radio frequency data in tracking the tissue motion and enabled the measurement of local deformation in both the vertical direction (orthogonal to the arm) and in the horizontal directions (parallel and perpendicular to direction of the arm) in two orthogonal cross sections of the muscle. The twitch experiments appeared to be reproducible in all three directions, and high strains in vertical (25 to 30%) and horizontal (Ϫ20% to Ϫ10%) directions were measured. Visual inspection of both the ultrasound data, as well as the strain data, revealed a relaxation that was significantly slower than the force decay. The pulse train experiments nicely illustrated the performance of our technique: 1) similar patterns of force and strain waveforms were found; and 2) each stimulation frequency yielded a different strain pattern, e.g., peak vertical strain was 40% during 10-Hz stimulation and 60% during 20-Hz stimulation. The voluntary contraction patterns were found to be both practically feasible and reproducible, which will enable muscles and more natural contraction patterns to be examined without the need of electrical stimulation.

Energy transfer between mitochondrial and cytosolic compartments is predominantly achieved by creatine-dependent phosphate shuttling (PCr/Cr) involving miCK. However ADP/ATP diffusion through adenine nucleotide translocase (ANT) and voltage-dependent anion carriers (VDAC) are also involved in this process. To determine if exercise alters the regulation of this system, ADP-stimulated mitochondrial respiratory kinetics were assessed in permeabilized muscle fibre bundles (PmFB) taken from biopsies before and after 2hr of cycling exercise (60% VO(2)peak) in 9 lean males. Concentrations of creatine (Cr) and phosphocreatine (PCr) as well as the contractile state of PmFB were manipulated in situ. In the absence of contractile signals (relaxed PmFB) and miCK activity (no Cr), post-exercise respiratory sensitivity to ADP was reduced in situ (up to 126% higher apparent K(m) to ADP) suggesting inhibition of ADP/ATP diffusion between matrix and cytosolic compartments (possibly ANT and VDAC). However this effect was masked in the presence of saturating Cr (no effect of exercise on ADP sensitivity). Given the role of ANT is thought to be independent of Cr, these findings suggest ADP/ATP, but not PCr/Cr, cycling through the outer mitochondrial membrane (VDAC) may be attenuated in resting muscle after exercise. In contrast, in contracted PmFB, post-exercise respiratory sensitivity to ADP increased with miCK activation (saturating Cr; 33% lower apparent (Km) to ADP), suggesting prior exercise increases miCK sensitivity in situ. These observations demonstrate that exercise increases miCK-dependent respiratory sensitivity to ADP, promoting mitochondrial-cytosolic energy exchange via PCr/Cr cycling, possibly through VDAC. This effect may mask an underlying inhibition of Cr-independent ADP/ATP diffusion. This enhanced regulation of miCK-dependent phosphate shuttling may improve energy homeostasis through more efficient coupling of oxidative phosphorylation to perturbations in cellular energy charge during subsequent bouts of contraction.

Aim:  The present study investigated the energy cost of lengthening, isometric and shortening contractions in rat muscle (n = 19).Methods:  With electrical stimulation the rat medial gastrocnemius muscle was maximally stimulated to perform 10 lengthening, isometric and shortening contractions (velocity 25 mm s−1) under experimental conditions (e.g. temperature, movement velocity) that resemble conditions in human movement.Results:  Mean ± SD force–time-integral of the first contraction was significantly different between the three protocols, 2.4 ± 0.2, 1.7 ± 0.2 and 1.0 ± 0.2 N s, respectively (P < 0.05). High-energy phosphate consumption was not significantly different between the three modes of exercise but a trend could be observed from lengthening (7.7 ± 2.7 μmol ∼ P muscle−1) to isometric (8.9 ± 2.2 μmol ∼ P muscle−1) to shortening contractions (10.4 ± 1.6 μmol ∼ P muscle−1). The ratio of high-energy phosphate consumption to force–time-integral was significantly lower for lengthening [0.3 ± 0.1 μmol ∼ P (N s)−1] and isometric [0.6 ± 0.2 μmol ∼ P (N s)−1] contractions compared with shortening [1.2 ± 0.2 μmol ∼ P (N s)−1] contractions (P < 0.05).Conclusion:  The present results of maximally stimulated muscles are comparable with data in the literature for voluntary human exercise showing that the energy cost of force production during lengthening exercise is ∼30% of that in shortening exercise. The present study suggests that this finding in humans probably does reflect intrinsic muscle properties rather than effects of differential recruitment and/or coactivation.

Background: Effects of extramuscular connective tissues on muscle force (experimentally measured) and lengths of sarcomeres (modeled) were investigated in rat. It was hypothesized that changes of muscle-relative position affect the distribution of lengths of sarcomeres within muscle fibers. Method of approach: The position of extensor digitorum longus muscle (EDL) relative to intact extramuscular connective tissues of the anterior crural compartment was manipulated without changing its muscle-tendon complex length. Results: Significant effects of EDL muscle relative position on proximal and distal EDL forces were found, indicating changes of extramuscular myofascial force transmission. EDL isometric force exerted at its proximal and distal tendons differed significantly. Finite-element modeling showed that the distribution of lengths of sarcomeres is altered by changes of muscle-relative position. Conclusions: It is concluded that forces exerted on a muscle via extramuscular myofascial pathways augment distributions of lengths of sarcomeres within that muscle.

Ever since it was first observed and especially so in recent years, the phenomenon of the so-called "sticking point'" in resistance training has attracted a substantial amount of sports and exercise science research. Broadly speaking the sticking point is understood as the position in the range-of-motion of a lift at which a disproportionately large increase in the difficulty to continue the lift is experienced. Hence the sticking point is inherently the performance bottleneck and is also associated with an increased chance of exercise form deterioration or breakdown. Understanding the aspects of lifting performance which should be analysed in order to pinpoint the cause of a specific sticking point and therefore devise an effective training strategy to overcome it, is of pervasive importance to strength practitioners and instrumental for the avoidance of injury and continued progress. In this paper we survey a range of physiological and biomechanical mechanisms which contribute to the development of sticking points, and led by this insight review and analyse the findings of the existing observational research on the occurrence of sticking points in three ubiquitous exercises: the bench press, the squat, and the deadlift. The findings of our analysis should be used to inform future research and current resistance training practice.

A spinal cord injury usually leads to an increase in contractile speed and fatigability of the paralysed quadriceps muscles, which is probably due to an increased expression of fast myosin heavy chain (MHC) isoforms and reduced oxidative capacity. Sometimes, however, fatigue resistance is maintained in these muscles and also contractile speed is slower than expected. To obtain a better understanding of the diversity of these quadriceps muscles and to determine the effects of training on characteristics of paralysed muscles, fibre characteristics and whole muscle function were assessed in six subjects with spinal cord lesions before and after a 12-week period of daily low-frequency electrical stimulation. Relatively high levels of MHC type I were found in three subjects and this corresponded with a high degree of fusion in 10-Hz force responses (r=0.88). Fatigability was related to the activity of succinate dehydrogenase (SDH) (r=0.79). Furthermore, some differentiation between fibre types in terms of metabolic properties were present, with type I fibres expressing the highest levels of SDH and lowest levels of a-glycerophosphate dehydrogenase. After training, SDH activity increased by 76€26% but fibre diameter and MHC expression remained unchanged. The results indicate that expression of contractile proteins and metabolic properties seem to underlie the relatively normal functional muscle characteristics observed in some paralysed muscles. Furthermore, training-induced changes in fatigue resistance seem to arise, in part, from an improved oxidative capacity.

Purpose This study investigates if co-ingestion of cluster dextrin (CDX) augments the appearance of intrinsically labeled meat protein hydrolysate-derived amino acid (D 5-phenylalanine), Akt/mTORC1 signaling, and myofibrillar protein fractional synthetic rate (FSR). Methods Ten moderately trained healthy males (age: 21.5 ± 2.1 years, body mass: 75.7 ± 7.6 kg, body mass index (BMI): 22.9 ± 2.1 kg/m 2) were included for a double-blinded randomized controlled crossover trial. Either 75 g of CDX or glucose (GLC) was given in conjunction with meat protein hydrolysate (0.6 g protein * FFM −1) following a whole-body resistance exercise. A primed-continuous intravenous infusion of L-[ 15 N]-phenylalanine with serial muscle biopsies and venous blood sampling was performed. Results A time × group interaction effect was found for serum D 5-phenylalanine enrichment (P < 0.01). Serum EAA and BCAA concentrations showed a main effect for group (P < 0.05). T max serum BCAA was greater in CDX as compared to GLC (P < 0.05). However, iAUC of all serum parameters did not differ between CDX and GLC (P > 0.05). T max serum EAA showed a trend towards a statistical significance favoring CDX over GLC. The phosphorylation of p70S6K Thr389 , rpS6 Ser240/244 , ERK1/2 Thr202/Tyr204 was greater in CDX compared to GLC (P < 0.05). However, postprandial myofibrillar FSR did not differ between CDX and GLC (P = 0.17). Conclusion In moderately trained younger males, co-ingestion of CDX with meat protein hydrolysate does not augment the postprandial amino acid availability or myofibrillar FSR as compared to co-ingestion of GLC during the recovery from a whole-body resistance exercise despite an increased intramuscular signaling. Trial registration ClinicalTrials.gov ID: NCT03303729 (registered on October 3, 2017).

1. The relationship between myosin heavy chain (MyHC) isoforms and high energy phosphate content was studied in human muscle fibres at rest and following maximal dynamic exercise lasting 25 s. 2. Single fibre fragments were characterized as type I, type IIA, type IIX or type IIAX.

Effects of two different training regimens on the contractile properties of the quadriceps muscle were studied in six individuals with spinal cord injury. Each subject had both limbs trained with the two regimens, consisting of stimulation with low frequencies (LF) at 10 HZ or high frequencies (HF) at 50 HZ; one limb of each subject was stimulated with the LF protocol and the other with the HF regimen. Twelve weeks of daily training increased tetanic tension by ∼20%, which was not significantly different between training regimens. Interestingly, after HF but not LF training, the unusual high forces at the low frequency range of the force-frequency relationship decreased, possibly due to a reduced activation per impulse. After LF but not HF training, force oscillation amplitudes declined (by 33%) as relaxation tended to slow, which may have opposed possible effects of reduced activation as seen after HF training. Finally, fatigue resistance also increased rapidly after LF training (by 43%) but not after HF training. These results indicate that different types of training may selectively change different aspects of function in disused muscles.

Physical exercise is important for people living under extreme environmental conditions
to stay healthy. Particularly in space, exercise counteracts the loss of muscle mass and
muscle strength caused by microgravity. Monitoring the adaptation of the
musculoskeletal system to assess muscle quality and devise individual training
programmes is highly desirable but is restricted by practical, technical and time
constraints on board the International Space Station (ISS). This study aimed to test the
feasibility of myometric measurements to monitor the mechanical properties of skeletal
muscles and tendons in weightlessness during parabolic flights.
The mechanical properties (frequency, decrement, stiffness relaxation time and creep)
of m. gastrocnemius, m. erector spinae and the Achilles tendon were assessed using
the MyotonPRO device in 11 healthy participants (aged 47 +/- 9 years) in normal
gravity as well as in microgravity during two parabolic flight campaigns. Results show
significant (p < .05-.001) changes in all mechanical properties of both muscles and the
Achilles tendon, indicating a more relaxed tissue state in microgravity. Recordings from
a phantom rubber material with the device in a test rig found changes between gravity
conditions that were too small (<1%) to explain the changes observed in the tissues.
It is concluded that myometric measurements are a feasible, easy to use and noninvasive
approach to monitor muscle health in extreme conditions that prohibit many
other methods. Real-time assessment of the quality of a muscle being exposed to the
negative effect of microgravity and also the positive effects of muscular training could
be achieved using Myoton technology.

The effect of prior submaximal exercise performed at two different pedalling frequencies, 60 and 120 rev'min -1, on maximal short-term power output (STPO) was investigated in seven male subjects during cycling exercise on an isokinetic cycle ergometer. Exercise of 6-min duration at a power output equivalent to 92 (SD 5)% maximal oxygen uptake (VO2max), whether performed at a pedalling frequency of 60 or 120 rev.min -1, reduced maximal STPO generated at 120 rev.min -1 to a much greater extent than maximal STPO at 60 rev" min-1. After 6-min submaximal exercise at 60 rev. min-1 mean reductions in maximal STPO measured at 120 and 60 rev.min -1 were 27 (SD 11)% and 15 (SD 9)% respectively, and were not significantly different from the reductions after exercise at 120 rev.min -1, 20 (SD 13)% and 5 (SD 9)%, respectively. In addition, we measured the effect of prior exercise performed at the same absolute external mechanical power output [236 (SD 30)W] with pedalling frequencies of 60 and 120 rev' min-1. Although the external power output was the same, the leg forces required (absolute as well as expressed as a proportion of the maximal leg force available at the same velocity) were much higher in prior exercise performed at 60 rev. rain-1. Nevertheless, maximal STPO generated at 120 rev. min-1 was reduced after exercise at 120 rev'min -1 [20 (SD 13)°/0, P<0.05] whereas no significant reduction in maximal STPO was found after prior exercise at 60 rev" min-1. The present findings would suggest that exercise performed at 92 (SD 5)% lkOzmax, whether at 60 or at 120 rev.min -1, selectively fatigues the faster fatigue-sensitive fibres resuiting in a greater reduction in maximal STPO generated at 120 compared to 60 rev.min -1. The greater fatigue of maximal STPO generated at 120 rev.min-1 due to exercise performed at a power output of 236 (SD 30)W at 120 rev'min -1 compared to 60 rev'min -1 would suggest a relatively greater contribution of fast fatigue-sensitive fibres when higher movement frequen-Correspondence to: A. Beelen, Department of Muscle and Exercise Physiology cies and hence different muscle shortening velocities are used at this submaximal exercise intensity.

A large corpus of data obtained by means of empirical study of neuromuscular adaptation is currently of limited use to athletes and their coaches. One of the reasons lies in the unclear direct practical utility of many individual trials. This paper introduces a mathematical model of adaptation to resistance training, which derives its elements from physiological fundamentals on the one side, and empirical findings on the other. The key element of the proposed model is what is here termed the athlete's capability profile. This is a generalization of length and velocity dependent force production characteristics of individual muscles, to an exercise with arbitrary biomechanics. The capability profile - a two-dimensional function over the capability plane - plays the central role in the proposed model of the training-adaptation feedback loop. Together with a dynamic model of resistance the capability profile is used in the model's predictive stage when exercise performance is simulated using a numerical approximation of differential equations of motion. Simulation results are used to infer the adaptational stimulus, which manifests itself through a fed back modification of the capability profile. It is shown how empirical evidence of exercise specificity can be formulated mathematically and integrated in this framework. A detailed description of the proposed model is followed by examples of its application - new insights into the effects of accommodating loading for powerlifting are demonstrated. This is followed by a discussion of the limitations of the proposed model and an overview of avenues for future work.

In literature, an inconsistency exists in the submaximal exercise intensity at which type II fibers are activated. In the present study, the recruitment of type I and II fibers was investigated from the very beginning and throughout a 45-min cycle exercise at 75% of the maximal oxygen uptake, which corresponded to 38% of the maximal dynamic muscle force. Biopsies of the vastus lateralis muscle were taken from six subjects at rest and during the exercise, two at each time point. From the first biopsy single fibers were isolated and characterized as type I and II, and phosphocreatine-to-creatine (PCr/ Cr) ratios and periodic acid-Schiff (PAS) stain intensities were measured. Cross sections were cut from the second biopsy, individual fibers were characterized as type I and II, and PAS stain intensities were measured. A decline in PCr/Cr ratio and in PAS stain intensity was used as indication of fiber recruitment. Within 1 min of exercise both type I and, although to a lesser extent, type II fibers were recruited. Furthermore, the PCr/Cr ratio revealed that the same proportion of fibers was recruited during the whole 45 min of exercise, indicating a rather constant recruitment. The PAS staining, however, proved inadequate to fully demonstrate fiber recruitment even after 45 min of exercise. We conclude that during cycling exercise a greater proportion of type II fibers is recruited than previously reported for isometric contractions, probably because of the dynamic character of the exercise. Furthermore, the PCr/Cr ratio method is more sensitive in determining fiber activation than the PAS stain intensity method.

The purpose of the study was to obtain force/velocity relationships for electrically stimulated (80 Hz) human adductor pollicis muscle (n = 6) and to quantify the effects of fatigue. There are two major problems of studying human muscle in situ; the first is the contribution of the series elastic component, and the second is a loss of force consequent upon the extent of loaded shortening. These problems were tackled in two ways. Records obtained from isokinetic releases from maximal isometric tetani showed a late linear phase of force decline, and this was extrapolated back to the time of release to obtain measures of instantaneous force. This method gave usable data up to velocities of shortening equivalent to approximately one-third of maximal velocity. An alternative procedure (short activation, SA) allowed the muscle to begin shortening when isometric force reached a value that could be sustained during shortening (essentially an isotonic protocol). At low velocities both protocols gave very similar data (r 2 = 0.96), but for high velocities only the SA procedure could be used. Results obtained using the SA protocol in fresh muscle were compared to those for muscle that had been fatigued by 25 s of ischaemic isometric contractions, induced by electrical stimulation at the ulnar nerve. Fatigue resulted in a decrease of isometric force [to 69 (3)%], an increase in half-relaxation time [to 431 (10)%], and decreases in maximal shortening velocity [to 77 (8)%] and power [to 42 (5)%]. These are the first data for human skeletal muscle to show convincingly that during acute fatigue, power is reduced as a consequence of both the loss of force and slowing of the contractile speed.

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, Myonectin and Fibronectin type III domain containing 5 (FNDC5), the precursor for Irisin. Methods. We performed immunoblot analysis and quantitative real-time PCR analysis of Myonectin and FNDC5 in the diaphragm muscles of obese Zucker rat (OZR) and lean Zucker rat (LZR) with 9 weeks of aerobic training on a motorized treadmill. Results. We show that myonectin gene expression is increased in the OZR model of obesity and decreases with exercise in both lean and obese Zucker rats. Conversely, myonectin protein concentration was elevated with exercise. Similarly, FNDC5 mRNA levels are significantly higher in the OZR, however exercise training had no effect on the expression level of FNDC5 in either the LZR or OZR. We did not observe any difference in muscle protein content of Irisin with obesity or exercise. Conclusion. Our data shows that exercise training does not increase either FNDC5 or myonectin gene expression, indicating that increased transcriptional regulation of these myokines is not induced by exercise. However, our data also indicates a yet to be explored disconnect between myonectin gene expression and protein content. Further, this report highlights the importance of verifying reference genes when completing gene expression analysis. We found that many commonly used reference genes varied significantly by obesity and/or exercise and would have skewed the results of this study if used to normalize gene expression data. The unstable reference genes include: beta-Actin, beta-2-microglobulin, Non-POU domain containing, octamer-binding, Peptidylprolyl isomerase H, 18S ribosomal RNA, TATA box binding protein and Transferrin receptor.

We have investigated the action of exogenous nitric oxide (NO) on the strength and contractile properties of human skeletal muscle working in vivo. Maximum isometric voluntary contraction force (MVC) of the quadriceps was measured and superimposed electrical stimulation was used to estimate the level of activation and`true maximum force' (TMF). Force±frequency relationships were determined to assess changes in contractile properties of the muscle. Subjects in the experimental group (E, n 10) were measured before and during two separate periods of treatment with different doses of glyceryl trinitrate, a NO donor, delivering 100 (GTN100) or 200 (GTN200) lg h ±1 as a transdermal patch. A control group (C, n 6) was measured during two similar periods whilst taking an oral placebo. There was a signi®cant increase in strength with GTN200 (MVC: +5.15%; TMF: +3.87%). There was no change in the strength of group C. There was a trend towards reduced forces at submaximal frequencies with GTN administration but the most notable change was a decline in twitch force (approximately 12%, P < 0.05) with GTN100 treatment and this remained depressed throughout the study. No changes were seen in the contractile properties of the control group C. The present results show that GTN treatment increased maximum voluntary strength but decreased twitch tension. The time course and dose±response characteristics indicate that these are two separate actions of NO on human muscle working in vivo.

Connective tissue formation following muscle injury and remedial surgery may involve changes in the stiffness and configuration of the connective tissues linking adjacent muscles. We investigated changes in mechanical interaction of muscles by implanting either a tissue-integrating mesh (n = 8) or an adhesion barrier (n = 8) to respectively increase or decrease the intermuscular connectivity between soleus muscle (SO) and the lateral gastrocnemius and plantaris complex (LG+PL) of the rat. As a measure of mechanical interaction, changes in SO tendon forces and proximal–distal LG+PL force differences in response to lengthening LG+PL proximally were assessed 1 and 2 weeks post-surgery. The extent of mechanical interaction was doubled 1 week post-implantation of the tissue-integrating mesh compared to an unaffected compartment (n = 8), and was more than four times higher 2 weeks post-surgery. This was found only for maximally activated muscles, but not when passive. Implanting the adhesion barrier did not result in a reduction of the mechanical interaction between these muscles. Our findings indicate that the ratio of force transmitted via myofascial, rather than myotendinous pathways, can increase substantially when the connectivity between muscles is enhanced. This improves our understanding of the consequences of connective tissue formation at the muscle boundary on skeletal muscle function.

Creatine supplementation has been found to significantly increase muscle strength and hypertrophy in young adults (≤ 35 yr) particularly when consumed in conjunction with a resistance training regime. Literature examining the efficacy of creatine supplementation in older adults (55-82 yr) suggests creatine to promote muscle strength and hypertrophy to a greater extent than resistance training alone. The following is a review of literature reporting on the effects of creatine supplementation on intramuscular high energy phosphates, skeletal muscle morphology and quality of life in older adults. Results suggest creatine supplementation to be a safe, inexpensive and effective nutritional intervention, particularly when consumed in conjunction with a resistance training regime, for slowing the rate of muscle wasting that is associated with aging. Physicians should strongly consider advising older adults to supplement with creatine and to begin a resistance training regime in an effort to enhance skeletal muscle strength and hypertrophy, resulting in enhanced quality of life.