Electrical stimulation to promote muscle and motor unit force and endurance after spinal cord injury.

Fatigue is a common feature of paralysed skeletal muscle, hindering performance when subjected to functional electrical stimulation (ES) for movement. We asked whether (1) 20 Hz ES for 5% of each day (2.5 s on and 2.5 s off for 3 h) increases tibialis anterior and medial gastrocnemius muscle and motor unit (MU) endurance after paralysis by hemisection and deafferentation (HSDA), and (2) muscle length or loading affects their isometric contractile properties. The daily 5% ES increased muscle endurance, largely independent of muscle length or loading, but to a lesser extent than the daily 50% ES (2.5 s on and 2.5 s off for 24 h). The former was effective in counteracting the decline and slowing of muscle force promoted by the 50% ES. The altered muscle properties were confirmed at the MU level in final experiments once the properties had plateaued. Fast-fatigable MUs were converted to fatigue-intermediate and -resistant MUs that finally comprised ∼80% as compared to ∼10% of the total MU number in the daily 5% ES and the control normal groups, respectively. We conclude that the daily 5% ES regimen counteracts the fatigue of paralysed muscle without compromising contractile force, and thereby, is effective in conditioning muscle for effective movement. KEY POINTS: We asked whether 20 Hz electrical stimulation (ES) for 5% of each day (2.5 s on and 2.5 s off for 3 h; 5% ES) preserves medial gastrocnemius and tibialis anterior muscle and MU isometric contractile forces and increases their endurance after paralysis. Daily 5% ES promoted increased muscle endurance irrespective of the muscle length or loading but to a lesser extent than daily 50% ES (20 Hz ES 2.5 s on and 2.5 s off for 24 h). 5% ES was effective in counteracting decline and slowing of muscle force that resulted from 50% ES. Motor units (MUs) were converted from fast fatigable to fatigue intermediate and resistant MUs, comprising ∼80% as compared to ∼10% in the control normal groups. We conclude that the 5% ES regimen counteracts the fatigue of paralysed muscle without compromising contractile force, and thereby is effective in conditioning the muscle for effective movement.

Effects of exercise prehabilitation on muscle atrophy and contractile properties in hindlimb-unloaded rats.

INTRODUCTION/AIMS: Effective strategies for rapid recovery after surgery are needed. Therefore, we investigated the effects of exercise prehabilitation (EP) and hindlimb unloading (HU) on muscle loss and contractility. METHODS: Twenty-two Sprague-Dawley rats (12 wk old) were divided into normal control (NCON, n = 5), hindlimb unloading control (HCON, n = 10), and exercise prehabilitation followed by hindlimb unloading (Ex-preH, n = 7) groups. Ex-PreH performed exercise training for 14 days before hindlimb unloading for 14 days. Body composition was evaluated, along with muscle strength and function. The soleus (SOL) and extensor digitorum longus (EDL) muscle contractile properties were analyzed at the whole-muscle level. The titin concentration and myosin heavy chain (MHC) type composition were analyzed. RESULTS: There were no effects of Ex-preH on total mass, lean mass, or muscle weight. Physical function was significantly higher in the Ex-preH group than in the HCON group (39.5° vs. 35.7°). The SOL twitch force (19.6 vs. 7.1 mN/m2 ) and specific force (107.3 vs. 61.2 mN/m2 ) were greater in Ex-preH group than in HCON group. EDL shortening velocity was higher in Ex-preH group than in HCON group (13.2 vs. 5.0 FL/s). The SOL full-length titin level was higher in Ex-preH group than in HCON group. DISCUSSION: Exercise prehabilitation did not prevent muscle mass loss followed by muscle wasting, although it minimized the reduction of physical function. Therefore, exercise prehabilitation should be considered for rapid functional recovery after disuse due to surgery and injuries.

Heat acclimation reduces the effects of whole-body hyperthermia on knee-extensor relaxation rate, but does not affect voluntary torque production.

PURPOSE: This study investigated the effects of acute hyperthermia and heat acclimation (HA) on maximal and rapid voluntary torque production, and their neuromuscular determinants. METHODS: Ten participants completed 10 days of isothermic HA (50 °C, 50% rh) and had their knee-extensor neuromuscular function assessed in normothermic and hyperthermic conditions, pre-, after 5 and after 10 days of HA. Electrically evoked twitch and octet (300 Hz) contractions were delivered at rest. Maximum voluntary torque (MVT), surface electromyography (EMG) normalised to maximal M-wave, and voluntary activation (VA) were assessed during brief maximal isometric voluntary contractions. Rate of torque development (RTD) and normalised EMG were measured during rapid voluntary contractions. RESULTS: Acute hyperthermia reduced neural drive (EMG at MVT and during rapid voluntary contractions; P < 0.05), increased evoked torques (P < 0.05), and shortened contraction and relaxation rates (P < 0.05). HA lowered resting rectal temperature and heart rate after 10 days (P < 0.05), and increased sweating rate after 5 and 10 days (P < 0.05), no differences were observed between 5 and 10 days. The hyperthermia-induced reduction in twitch half-relaxation was attenuated after 5 and 10 days of HA, but there were no other effects on neuromuscular function either in normothermic or hyperthermic conditions. CONCLUSION: HA-induced favourable adaptations to the heat after 5 and 10 days of exposure, but there was no measurable benefit on voluntary neuromuscular function in normothermic or hyperthermic conditions. HA did reduce the hyperthermic-induced reduction in twitch half-relaxation time, which may benefit twitch force summation and thus help preserve voluntary torque in hot environmental conditions.

Mechanisms underlying altered neuromuscular function in people with DPN.

Diabetes alters numerous physiological functions and can lead to disastrous consequences in the long term. Neuromuscular function is particularly affected and is impacted early, offering an opportunity to detect the onset of diabetes-related dysfunctions and follow the advancement of the disease. The role of physical training for counteracting the deleterious effects of diabetes is well accepted but at the same time, it appears difficult to reliably assess the effects of exercise on functional capacity in patients with diabetic peripheral neuropathy (DPN). In this paper, we will review the specific characteristics of various neuromuscular dysfunctions associated with diabetes according to the DPN presence or not, and their changes over time. We present several propositions regarding the onset of neuromuscular alterations in people with diabetes compared to people with DPN. It appears that motor unit loss and neuromuscular transmission impairment are among the main mechanisms explaining the considerable degradation of neuromuscular function in the transition from a diabetic to neuropathic state. Rate of force development and contractile properties could start to decrease with the onset of preferential type II fiber atrophy, commonly reported in people with DPN. Finally, Mmax amplitude could decrease with neuromuscular fatigue only in people with DPN, reflecting the fatigue-related neuromuscular transmission impairment reported in people with DPN. In this review, we show that the different neuromuscular parameters are altered at different stages of diabetes, according to the presence of DPN or not. The precise evaluation of these parameters might participate in adapting the physical training prescription.

Weakened Contractile Performance and Mitochondrial Respiratory Complex Activity in Skeletal Muscle Improve during Interbout Arousal in Hibernating Daurian Ground Squirrel, Spermophilus dauricus.

Mammalian hibernation is composed of multiple episodes of torpor bout, separated by phases of interbout arousal. During torpor, the skeletal muscles of mammals are undoubtedly inactive, but it has been proven to mitigate disuse atrophy. While interbout arousal has been implicated in the prevention of muscle atrophy, the underlying mechanisms sustaining muscle contraction remain to be explored. In the present study, Daurian ground squirrels (Spermophilus dauricus) were divided into four groups: pre-hibernation (PRE), torpor (TOR), interbout arousal (IBA), and post-hibernation (POST). The contractile performance of slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL) was detected both in situ and in vitro. Concurrently, mitochondrial respiratory chain complex activity in these muscles was quantified. Our findings revealed that in situ contractile properties of both muscles, including force, power output, time duration, and force development/relaxation rates of twitch contraction, and force and power output of tetanic contraction declined in the TOR group compared to the PRE group, but improved in the IBA and POST groups. Fatigue resistance of muscles, determined by the power output of repetitive tetanic contractions in situ, decreased in the TOR group but recovered in the IBA and POST groups. In vitro studies demonstrated that tetanic contraction power output in isolated muscles increased with muscle temperature in both TOR and IBA groups. However, at the same temperature, power output was consistently lower in the TOR group compared to the IBA group. Moreover, the activity of the mitochondrial respiratory chain complex, especially Complexes I and II, decreased in the TOR group but showed recovery in the IBA and POST groups. These findings suggest that both the contractile performance and fatigue resistance of mammalian skeletal muscle are compromised during torpor but can be improved during interbout arousal and post-hibernation. The rebound in body temperature and rise in mitochondrial respiratory chain complex activity in skeletal muscle are involved in enhancing contractile performance and fatigue resistance. This study suggests that interbout arousal functions as a vital temporal interval during which skeletal muscles can transition from the inactivity induced by torpor to a state of restored contractile functionality. Thus, interbout arousal serves as a behavioral safeguard against disuse-induced damage to skeletal muscles during hibernation.

The RyR1 P3528S Substitution Alters Mouse Skeletal Muscle Contractile Properties and RyR1 Ion Channel Gating.

The recessive Ryanodine Receptor Type 1 (RyR1) P3527S mutation causes mild muscle weakness in patients and increased resting cytoplasmic [Ca2+] in transformed lymphoblastoid cells. In the present study, we explored the cellular/molecular effects of this mutation in a mouse model of the mutation (RyR1 P3528S). The results were obtained from 73 wild type (WT/WT), 82 heterozygous (WT/MUT) and 66 homozygous (MUT/MUT) mice with different numbers of observations in individual data sets depending on the experimental protocol. The results showed that WT/MUT and MUT/MUT mouse strength was less than that of WT/WT mice, but there was no difference between genotypes in appearance, weight, mobility or longevity. The force frequency response of extensor digitorum longus (EDL) and soleus (SOL) muscles from WT/MUT and MUT/MUT mice was shifter to higher frequencies. The specific force of EDL muscles was reduced and Ca2+ activation of skinned fibres shifted to a lower [Ca2+], with an increase in type I fibres in EDL muscles and in mixed type I/II fibres in SOL muscles. The relative activity of RyR1 channels exposed to 1 µM cytoplasmic Ca2+ was greater in WT/MUT and MUT/MUT mice than in WT/WT mice. We suggest the altered RyR1 activity due to the P2328S substitution could increase resting [Ca2+] in muscle fibres, leading to changes in fibre type and contractile properties.

A comparison of thermal sensitivities of wing muscle contractile properties from a temperate and tropical bat species.

Endotherms experience temperature variation among body regions, or regional heterothermy, despite maintaining high core body temperatures. Bat forelimbs are elongated to function as wings, which makes them vulnerable to heat loss and exaggerates regional heterothermy. A tropical bat species, Carollia perspicillata, flies with distal wing muscles that are substantially (>10°C) cooler than proximal wing muscles and significantly less temperature sensitive. We hypothesized that the difference between proximal and distal wing muscles would be even more extreme in a temperate bat species that is capable of flight at variable environmental temperatures. We measured the contractile properties of the proximal pectoralis muscle and distal extensor carpi radialis muscle at a range of temperatures in the big brown bat, Eptesicus fuscus, and compared their thermal dependence with that of the same muscles in C. perspicillata. We found that, overall, temperature sensitivities between species were remarkably similar. The sole exception was the shortening velocity of the pectoralis muscle in E. fuscus, which was less temperature sensitive than in C. perspicillata. This decreased temperature sensitivity in a proximal muscle runs counter to our prediction. We suggest that the relative lability of body temperature in E. fuscus may make better pectoralis function at low temperatures advantageous.

Short-term effects of two different recovery strategies on muscle contractile properties in healthy active men: A randomised cross-over study.

The aim of this study was to compare the immediate effects of cold-water immersion (CWI) and hot-water immersion (HWI) versus passive resting after a fatigue-induced bout of exercise on the muscle contractile properties of the Vastus Medialis (VM). We conducted a randomised cross-over study involving 28 healthy active men where muscle contractile properties of the VM wer recorded using Tensiomyography (TMG) before and after CWI, HWI or passive resting and up to one-hour post-application. The main outcomes obtained were muscle displacement and velocity of deformation according to limb size (Dmr and Vdr). Our results showed a significant effect of time (F(3.9,405) =32.439; p <0.001; η2p =0.29) and the interaction between time and temperature (F(7.9,405) =5.814; p <0.001; η2p=0.13) on Dmr but no for temperature alone (F(2,81) =2.013; p =0.14; η2p=0.04) while for Vdr, both time (F(5.2,486) =23.068; p <0.001 η2p = 0.22) and temperature (F(2,81) =4.219; p = 0.018; η2p= 0.09) as well as the interaction (F(10.4,486) =7.784; p <0.001; η2p =0.16) were found significant. Compared to CWI, HWI increased Dmr post-application and Vdr both post-application as well as 15 and 45' thereafter. These findings suggest that applying HWI could be a valid alternative to CWI to promote muscle recovery.

Krüppel-like factor 10 regulates the contractile properties of skeletal muscle fibers in mice.

INTRODUCTION/AIMS: Klf10 is a member of the Krüppel-like family of transcription factors, which is implicated in mediating muscle structure (fiber size, organization of the sarcomere), muscle metabolic activity (respiratory chain), and passive force. The aim of this study was to further characterize the roles of Klf10 in the contractile properties of skeletal muscle fibers. METHODS: Fifty-two single fibers were extracted from female wild-type (WT) and Klf10 knockout (KO) oxidative (soleus) and glycolytic (extensor digitorum longus [EDL]) skinned muscles. Each fiber was immersed successively in relaxing (R), washing (W), and activating (A) solutions. Calcium was included in the activating solution to induce a maximum contraction of the fiber. The maximum force (Fmax ) was measured and normalized to the cross-sectional area to obtain the maximum stress (Stressmax ). After a steady state in contraction was reached, a quick stretch-release was performed; the force at the maximum stretch (Fstretch ) was measured and the stiffness was assessed. RESULTS: Deletion of the Klf10 gene induced changes in the contractile parameters (Fmax , Stressmax , Stiffness), which were lower and higher for soleus and EDL fibers compared with littermates, respectively. These measurements also revealed changes in the proportion and resistance of attached cross-bridges. DISCUSSION: Klf10 plays a major role in the homeostasis of the contractile behavior of skeletal muscle fibers in a muscle fiber type-specific manner. These findings further implicate important roles for Klf10 in skeletal muscle function and shed new light on understanding the molecular processes regulating the contractility of skeletal muscle fibers.

Acute effects of dynamic stretching on neuromechanical properties: an interaction between stretching, contraction, and movement.

PURPOSE: The present study aimed to investigate the acute effects of dynamic stretching on neurophysiological and mechanical properties of plantar flexor muscles and to test the hypothesis that dynamic stretching resulted from an interaction between stretching, movement, and contraction. METHODS: The dynamic stretching conditioning activity (DS) was compared to static stretching (SS), passive cyclic stretching (PCS), isometric contractions (IC), static stretching followed by isometric contractions (SSIC), and control (CO) conditions. Stretching amplitude (DS, SS, PCS and SSIC), contraction intensity (DS, IC and SSIC) and duration (all 6 conditions) were matched. Thirteen volunteers were included. Passive torque, fascicle length, and stiffness were evaluated from a dynamometer and ultrasonography during passive dorsiflexion. Neuromuscular electrical stimulation was used to investigate contractile properties [peak twitch torque (PTT), and rate of torque development (RTD)] and muscle voluntary activation (%VA). Gastrocnemius lateralis electromyographic activity (GL EMG/Mwave) was obtained during maximal voluntary contraction. All of these parameters were measured immediately before and 10 s after each experimental condition. RESULTS: Peak twitch torque, RTD, %VA, GL EMG/Mwave remained unaltered, while passive torque was significantly reduced after DS (- 8.14 ± 2.21%). SS decreased GL EMG/Mwave (- 7.83 ± 12.01%) and passive torque (- 2.16 ± 7.25%). PCS decreased PTT (- 3.40 ± 6.03%), RTD (- 2.96 ± 5.16%), and passive torque (- 2.16 ± 2.05%). IC decreased passive torque (- 7.72 ± 1.97%) and enhanced PTT (+ 5.77 ± 5.19%) and RTD (+ 7.36 ± 8.35%). However, SSIC attenuated PTT and RTD improvements as compared to IC. CONCLUSION: These results suggested that dynamic stretching is multi-component and would result from an interaction between stretching, contraction, and movement.

Indirect evidence that anoxia exposure and cold acclimation alter transarcolemmal Ca2+ flux in the cardiac pacemaker, right atrium and ventricle of the red-eared slider turtle (Trachemys scripta).

We indirectly assessed if altered transarcolemmal Ca2+ flux accompanies the decreased cardiac activity displayed by Trachemys scripta with anoxia exposure and cold acclimation. Turtles were first acclimated to 21 °C or 5 °C and held under normoxic (21N; 5N) or anoxic conditions (21A; 5A). We then compared the response of intrinsic heart rate (fH) and maximal developed force of spontaneously contracting right atria (Fmax,RA), and maximal developed force of isometrically-contracting ventricular strips (Fmax,V), to Ni2+ (0.1-10 mM), which respectively blocks T-type Ca2+ channels, L-type Ca2+ channels and the Na+-Ca2+-exchanger at the low, intermediate and high concentrations employed. Dose-response curves were established in simulated in vivo normoxic (Sim Norm) or simulated in vivo anoxic extracellular conditions (Sim Anx; 21A and 5A preparations). Ni2+ decreased intrinsic fH, Fmax,RA and Fmax,V of 21N tissues in a concentration-dependent manner, but the responses were blunted in 21A tissues in Sim Norm. Similarly, dose-response curves for Fmax,RA and Fmax,V of 5N tissues were right-shifted, whereas anoxia exposure at 5 °C did not further alter the responses. The influence of Sim Anx was acclimation temperature-, cardiac chamber- and contractile parameter-dependent. Combined, the findings suggest that: (1) reduced transarcolemmal Ca2+ flux in the cardiac pacemaker is a potential mechanism underlying the slowed intrinsic fH of anoxic turtles at 21 °C, but not 5 °C, (2) a downregulation of transarcolemmal Ca2+ flux may aid cardiac anoxia survival at 21 °C and prime the turtle myocardium for winter anoxia and (3) confirm that altered extracellular conditions with anoxia exposure can modify turtle cardiac transarcolemmal Ca2+ flux.

Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids.

Numerous protocols of cardiac differentiation have been established by essentially focusing on specific growth factors on human pluripotent stem cell (hPSC) differentiation efficiency. However, the optimal environmental factors to obtain cardiac myocytes in network are still unclear. The mesoderm germ layer differentiation is known to be enhanced by low oxygen exposure. Here, we hypothesized that low oxygen exposure enhances the molecular and functional maturity of the cardiomyocytes. We aimed at comparing the molecular and functional consequences of low (5% O2 or LOE) and high oxygen exposure (21% O2 or HOE) on cardiac differentiation of hPSCs in 2D- and 3D-based protocols. hPSC-CMs were differentiated through both the 2D (monolayer) and 3D (embryoid body) protocols using several lines. Cardiac marker expression and cell morphology were assessed. The mitochondrial localization and metabolic properties were evaluated. The intracellular Ca2+ handling and contractile properties were also monitored. The 2D cardiac monolayer can only be differentiated in HOE. The 3D cardiac spheroids containing hPSC-CMs in LOE further exhibited cardiac markers, hypertrophy, steadier SR Ca2+ release properties revealing a better SR Ca2+ handling, and enhanced contractile force. Preserved distribution of mitochondria and similar oxygen consumption by the mitochondrial respiratory chain complexes were also observed. Our results brought evidences that LOE is moderately beneficial for the 3D cardiac spheroids with hPSC-CMs exhibiting further maturity. In contrast, the 2D cardiac monolayers strictly require HOE.

Ca2+ dependency of limb muscle fiber contractile mechanics in young and older adults.

Age-induced declines in skeletal muscle contractile function have been attributed to multiple cellular factors, including lower peak force (Po), decreased Ca2+ sensitivity, and reduced shortening velocity (Vo). However, changes in these cellular properties with aging remain unresolved, especially in older women, and the effect of submaximal Ca2+ on contractile function is unknown. Thus, we compared contractile properties of muscle fibers from 19 young (24 ± 3 yr; 8 women) and 21 older adults (77 ± 7 yr; 7 women) under maximal and submaximal Ca2+ and assessed the abundance of three proteins thought to influence Ca2+ sensitivity. Fast fiber cross-sectional area was ~44% larger in young (6,479 ± 2,487 µm2) compared with older adults (4,503 ± 2,071 µm2, P < 0.001), which corresponded with a greater absolute Po (young = 1.12 ± 0.43 mN; old = 0.79 ± 0.33 mN, P < 0.001). There were no differences in fast fiber size-specific Po, indicating the age-related decline in force was explained by differences in fiber size. Except for fast fiber size and absolute Po, no age or sex differences were observed in Ca2+ sensitivity, rate of force development (ktr), or Vo in either slow or fast fibers. Submaximal Ca2+ depressed ktr and Vo, but the effects were not altered by age in either sex. Contrary to rodent studies, regulatory light chain (RLC) and myosin binding protein-C abundance and RLC phosphorylation were unaltered by age or sex. These data suggest the age-associated reductions in contractile function are primarily due to the atrophy of fast fibers and that caution is warranted when extending results from rodent studies to humans.

Impaired exercise performance is independent of inflammation and cellular stress following genetic reduction or deletion of selenoprotein S.

Selenoprotein S (Seps1) can be protective against oxidative, endoplasmic reticulum (ER), and inflammatory stress. Seps1 global knockout mice are less active, possess compromised fast muscle ex vivo strength, and, depending on context, heightened inflammation. Oxidative, ER, and inflammatory stress modulates contractile function; hence, our aim was to investigate the effects of Seps1 gene dose on exercise performance. Seps1-/- knockout, Seps1-/+ heterozygous, and wild-type mice were randomized to 3 days of incremental, high-intensity treadmill running or a sedentary control group. On day 4, the in situ contractile function of fast tibialis anterior (TA) muscles was determined. Seps1 reduction or deletion compromised exercise capacity, decreasing distance run. TA strength was also reduced. In sedentary Seps1-/- knockout mice, TA fatigability was greater than wild-type mice, and this was ameliorated with exercise. Whereas, in Seps1+/- heterozygous mice, exercise compromised TA endurance. These impairments in exercise capacity and TA contractile function were not associated with increased inflammation or a dysregulated redox state. Seps1 is highly expressed in muscle fibers and blood vessels. Interestingly, Nos1 and Vegfa mRNA transcripts were decreased in TA muscles from Seps1-/- knockout and Seps1-/+ heterozygous mice. Impaired exercise performance with Seps1 reduction or deletion cannot be attributed to heightened cellular stress, but it may potentially be mediated, in part, by the effects of Seps1 on the microvasculature.

Toxic doses of caffeine are needed to increase skeletal muscle contractility.

Discrepant results have been reported regarding an intramuscular mechanism underlying the ergogenic effect of caffeine on neuromuscular function in humans. Here, we reevaluated the effect of caffeine on muscular force production in humans and combined this with measurements of the caffeine dose-response relationship on force and cytosolic free [Ca2+] ([Ca2+]i) in isolated mouse muscle fibers. Twenty-one healthy and physically active men (29 ± 9 yr, 178 ± 6 cm, 73 ± 10 kg, mean ± SD) took part in the present study. Nine participants were involved in two experimental sessions during which supramaximal single and paired electrical stimulations (at 10 and 100 Hz) were applied to the femoral nerve to record evoked forces. Evoked forces were recorded before and 1 h after ingestion of 1) 6 mg caffeine/kg body mass or 2) placebo. Caffeine plasma concentration was measured in 12 participants. In addition, submaximal tetanic force and [Ca2+]i were measured in single mouse flexor digitorum brevis (FDB) muscle fibers exposed to 100 nM up to 5 mM caffeine. Six milligrams of caffeine per kilogram body mass (plasma concentration ~40 µM) did not increase electrically evoked forces in humans. In superfused FDB single fibers, millimolar caffeine concentrations (i.e., 15- to 35-fold above usual concentrations observed in humans) were required to increase tetanic force and [Ca2+]i. Our results suggest that toxic doses of caffeine are required to increase muscle contractility, questioning the purported intramuscular ergogenic effect of caffeine in humans.

Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis.

Gut microbiota is involved in the development of several chronic diseases, including diabetes, obesity, and cancer, through its interactions with the host organs. It has been suggested that the cross talk between gut microbiota and skeletal muscle plays a role in different pathological conditions, such as intestinal chronic inflammation and cachexia. However, it remains unclear whether gut microbiota directly influences skeletal muscle function. In this work, we studied the impact of gut microbiota modulation on mice skeletal muscle function and investigated the underlying mechanisms. We determined the consequences of gut microbiota depletion after treatment with a mixture of a broad spectrum of antibiotics for 21 days and after 10 days of natural reseeding. We found that, in gut microbiota-depleted mice, running endurance was decreased, as well as the extensor digitorum longus muscle fatigue index in an ex vivo contractile test. Importantly, the muscle endurance capacity was efficiently normalized by natural reseeding. These endurance changes were not related to variation in muscle mass, fiber typology, or mitochondrial function. However, several pertinent glucose metabolism markers, such as ileum gene expression of short fatty acid chain and glucose transporters G protein-coupled receptor 41 and sodium-glucose cotransporter 1 and muscle glycogen level, paralleled the muscle endurance changes observed after treatment with antibiotics for 21 days and reseeding. Because glycogen is a key energetic substrate for prolonged exercise, modulating its muscle availability via gut microbiota represents one potent mechanism that can contribute to the gut microbiota-skeletal muscle axis. Taken together, our results strongly support the hypothesis that gut bacteria are required for host optimal skeletal muscle function.

Extensive eccentric contractions in intact cardiac trabeculae: revealing compelling differences in contractile behaviour compared to skeletal muscles.

Force enhancement (FE) is a phenomenon that is present in skeletal muscle. It is characterized by progressive forces upon active stretching-distinguished by a linear rise in force-and enhanced isometric force following stretching (residual FE (RFE)). In skeletal muscle, non-cross-bridge (XB) structures may account for this behaviour. So far, it is unknown whether differences between non-XB structures within the heart and skeletal muscle result in deviating contractile behaviour during and after eccentric contractions. Thus, we investigated the force response of intact cardiac trabeculae during and after isokinetic eccentric muscle contractions (10% of maximum shortening velocity) with extensive magnitudes of stretch (25% of optimum muscle length). The different contributions of XB and non-XB structures to the total muscle force were revealed by using an actomyosin inhibitor. For cardiac trabeculae, we found that the force-length dynamics during long stretch were similar to the total isometric force-length relation. This indicates that no (R)FE is present in cardiac muscle while stretching the muscle from 0.75 to 1.0 optimum muscle length. This finding is in contrast with the results obtained for skeletal muscle, in which (R)FE is present. Our data support the hypothesis that titin stiffness does not increase with activation in cardiac muscle.

Explosive strength: effect of knee-joint angle on functional, neural, and intrinsic contractile properties.

PURPOSE: The present study compared knee extension explosive isometric torque, neuromuscular activation, and intrinsic contractile properties at five different knee-joint angles (35°, 50°, 65°, 80°, and 95°; 0° = full knee extension). METHODS: Twenty-eight young healthy males performed two experimental sessions each involving: 2 maximum, and 6-8 explosive voluntary contractions at each angle; to measure maximum voluntary torque (MVT), explosive voluntary torque (EVT; 50-150 ms after contraction onset) and quadriceps surface EMG (QEMG, 0-50, 0-100, and 0-150 ms after EMG onset during the explosive contractions). Maximum twitch and M-wave (MMAX) responses as well as octet contractions were evoked with femoral nerve stimulation at each angle. RESULTS: Absolute MVT and EVT showed an inverted 'U' relationship with higher torque at intermediate angles. There were no differences between knee-joint angles for relative EVT (%MVT) during the early phase (≤ 75 ms) of contraction and only subtle differences during the late phase (≥ 75 ms) of contraction (≤ 11%). Neuromuscular activation during explosive contractions was greater at more flexed than extended positions, and this was also the case during MVT. Whilst relative twitch torque (%MVT) was higher at knee flexed positions (P ≤ 0.001), relative octet torque (%MVT) was higher at knee extended positions (P ≤ 0.001). CONCLUSION: Relative EVT was broadly similar between joint angles, likely because neuromuscular activation during both explosive and plateau (maximum) phases of contraction changed proportionally, and due to the opposing changes in twitch and octet evoked responses with joint angle.

Is the joint-angle specificity of isometric resistance training real? And if so, does it have a neural basis?

PURPOSE: There are suggestions that isometric resistance training (RT) produces highly angle-specific changes in strength with the greatest changes at the training angle, but these effects remain controversial with limited rigorous evidence, and the possible underpinning physiological mechanism(s) remain opaque. This study investigated the extent of angle-specific changes in strength and neuromuscular activation after RT in comparison to a control group. METHODS: A RT group (n = 13) performed 14 isometric RT sessions at a knee-joint angle of 65° (0° is anatomical position) over a 4-week period, whilst a control group (CON, n = 9) maintained their habitual activity. Pre- and post-test sessions involved voluntary and evoked isometric knee extension contractions at five knee-joint angles (35°, 50°, 65°, 80° and 95°), while electromyography was recorded. RESULTS: RT group increased maximum voluntary torque (MVT) at the training angle (65°; + 12%) as well as 80° (+ 7%), 50° (+ 11%) and 35° (+ 5%). Joint-angle specificity was demonstrated within the RT group (MVT increased more at some angles vs. others), and also by more rigorous between-group comparisons (i.e., larger improvements after RT vs. CON at some angles than others). For the RT group, normalized EMG increased at three of the same joint angles as strength, but not for CON. Importantly, however, neither within- or between-group analyses provided evidence of joint angle-specific changes in activation. CONCLUSION: In conclusion, this study provides robust evidence for joint angle-specific strength gains after isometric RT, with weaker evidence that changes in neuromuscular activation may contribute to these adaptations.

Characterization of torque generating properties of ankle plantar flexor muscles in ambulant adults with cerebral palsy.

PURPOSE: Weakness of plantar flexor muscles is related to reduced push-off and forward propulsion during gait in persons with cerebral palsy (CP). It has not been clarified to what an extent altered muscle contractile properties contribute to this muscle weakness. Here, we investigated the torque generating capacity and muscle fascicle length in the triceps surae muscle throughout ankle range of motion (ROM) in adults with CP using maximal single muscle twitches elicited by electrical nerve stimulation and ultrasonography. METHODS: Fourteen adults with CP (age 36, SD 10.6, GMFCS I-III) and 17 neurological intact (NI) adults (age 36, SD 4.5) participated. Plantar flexor torque during supramaximal stimulation of the tibial nerve was recorded in a dynamometer at 8 ankle angles throughout ROM. Medial gastrocnemius (MG) fascicle length was tracked using ultrasonography. RESULTS: Adults with CP showed reduced plantar flexor torque and fascicle shortening during supramaximal stimulation throughout ROM. The largest torque generation was observed at the ankle joint position where the largest shortening of MG fascicles was observed in both groups. This was at a more plantarflexed position in the CP group. CONCLUSION: Reduced torque and fascicle shortening during supramaximal stimulation of the tibial nerve indicate impaired contractile properties of plantar flexor muscles in adults with CP. Maximal torque was observed at a more plantarflexed position in adults with CP indicating an altered torque-fascicle length/ankle angle relation. The findings suggest that gait rehabilitation in adults with CP may require special focus on improvement of muscle contractility.