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Background: Pork quality is affected by the type of muscle fibers, which is closely related to meat color, tenderness and juiciness. Exosomes are tiny vesicles with a diameter of approximately 30–150 nm that are secreted by cells and taken up by recipient cells to mediate communication. Exosome-mediated muscle-fat tissue crosstalk is a newly discovered mechanism that may have an important effect on intramuscular fat deposition and with that on meat quality. Various of adipose tissue-derived exosomes have been discovered and identified, but the identification and function of muscle exosomes, especially porcine fast/slow myotube exosomes, remain unclear. Here, we first isolated and identified exosomes secreted from porcine extensor digitorum longus (EDL) and soleus (SOL), which represent fast and slow muscle, respectively, and further explored their effects on lipid accumulation in longissimus dorsi adipocytes. Results: Porcine SOL-derived exosomes (SOL-EXO) and EDL-derived exosomes (EDL-EXO) were first identified and their average particle sizes were approximately 84 nm with double-membrane disc- shapes as observed via transmission electron microscopy and scanning electron microscopy. Moreover, the intramuscular fat content of the SOL was greater than that of the EDL at 180 days of age, because SOL intramuscular adipocytes had a stronger lipid-accumulating capacity than those of the EDL. Raman spectral analysis revealed that SOL-EXO protein content was much greater than that of EDL-EXO. Proteomic sequencing identified 72 proteins that were significantly differentially expressed between SOL-EXO and EDL-EXO, 31 of which were downregulated and 41 of which were upregulated in SOL-EXO. Conclusions: Our findings suggest that muscle-fat tissue interactions occur partly via SOL-EXO promoting adipogenic activity of intramuscular adipocytes. [ABSTRACT FROM AUTHOR]

Folic acid fortification of all white flour, enriched pasta, and cornmeal products became mandatory in Canada to reduce risk of neural tube defects at birth. Furthermore, Health Canada and the Society of Obstetricians and Gynaecologists of Canada recommend women take daily prenatal folic acid supplements in addition to folic acid fortified foods during pregnancy. However, the influence of maternal folic acid supplementation on offspring development, specifically the highly abundant and metabolically active skeletal muscle, is currently unknown. Thus, the purpose of this study was to determine the effect of supplemental folic acid (four times higher than normal dietary consumption), in utero and throughout suckling on muscle size, function, and metabolism in male and female CD-1 mouse offspring. The major findings were that maternal exposure to supplemental folic acid (i) had no impact on postpartum growth rates or muscle mass in female and male offspring, (ii) had no impact on skeletal muscle contractile kinetics in females and male offspring, and (iii) increased maximal phosphofructokinase activity in extensor digitorum longus of female and male offspring. These findings suggest that exposure to folic acid supplementation in utero and throughout suckling at levels four times higher than recommended had minimal effect on skeletal muscle size, function, and metabolism regardless of sex. Future research is needed explore the underlying biological pathways and mechanisms affected by folic acid supplementation during pregnancy and lactation on offspring skeletal muscle tissue, specifically in humans. [ABSTRACT FROM AUTHOR]

Objectives: To describe the morphological characteristics of subfascial intermuscular adipose tissue (IMATS) in the anterior compartment of the leg, considering its developmental and functional relationship with the crural fascia. Methods: In twenty formalin-fixed cadaveric legs (13 males, 7 females), after removal of the skin and crural fascia, the IMATS was exposed and classified into four types according to its shape. Leg length was divided into eight regions. The length, width at the widest point, closest distances of the upper and lower ends to the intermalleolar line and the anterior margin of the tibia, as well as the thickness of the skin-subcutaneous tissue complex, limb and leg lengths were measured for IMATS. Results: The most common type of IMATS was the short-large type. The largest point of IMATS was located in zone 3 or 4, and this point was located in the two zones closest to the lower end of IMATS in 75% of cases. In all cases, one to three connecting vessels piercing the crural fascia (80% were in zones 2, 3 or 4) connected to the IMATS in a slightly lateral to medial oblique course of the IMATS from top to bottom. The IMATS was superficially located in the tendinous and muscular parts of the extensor digitorum longus and/or tibialis anterior muscles, loosely attached to the muscles and crural fascia, but not between the muscle fibers. Although the largest point (p=0.041) and the distance from the distal end to the anterior margin of the tibia were found to be greater in males (p=0.049), the gender difference disappeared when normalized for limb length. Conclusion: No data on IMATS morphometry could be found in the literature. A remarkable finding of the study, which is open to interpretation in terms of the function of the IMATS, is that the location of the IMATS overlaps with the crural fascia region, which is reported to be biomechanically stiffer in the transverse direction. Our data that a connecting vessel is always connected to the IMATS by a fixed spatial relationship strengthens the argument that the developmental history of both structures may intersect. [ABSTRACT FROM AUTHOR]

Featured Application: Awareness of the role of the extensor digitorum longus can point to rehabilitation treatment and functional surgery towards more effective solutions. Equinus and equinovarus foot deviations (EVFD) are the most frequent lower limb acquired deformities in stroke survivors. We analysed the contribution that the tibialis anterior (TA), extensor digitorum longus (EDL) and plantarflexor muscles play in EVFD via a biomechanical musculoskeletal model of the ankle–foot complex. Our model was composed of 28 bones (connected by either revolute joints or bone surface contacts), 15 ligaments (modelled as non-linear springs), and 10 muscles, modelled as force actuators. Different combinations of muscle contractions were also simulated. Our results demonstrate that, compared to the condition when the foot is suspended off the ground, the contraction of the TA alone produces dorsiflexion (from −18° to 0°) and a greater supination/inversion (from 12° to 30°). The EDL alone produces dorsiflexion (from −18° to −6°), forefoot pronation (25°) and calcaneal eversion (5.6°). Only TA and EDL synergistic action can lead the foot to dorsiflexion suitable for most daily life activities (≥20°) without any deviation in the frontal plane. When pathological contractures of the plantarflexor muscles were simulated, foot deformities reproducing EVFD were obtained. These results can be relevant for clinical applications, highlighting the importance of EDL assessment, which may help to design appropriate functional surgery and plan targeted rehabilitation treatments. [ABSTRACT FROM AUTHOR]

Postactivation potentiation refers to an acute enhancement of contractile properties following muscle activity. Previously, the effects of prior muscle activation on eccentric force at tetanic activation frequencies have only been sparsely reported. This paper aimed to study acute activity-induced effects on eccentric force of slow and fast-twitch muscles and characterize them in relation to postactivation potentiation. We elicited eccentric contractions in isolated rat extensor digitorum longus and soleus muscles by actively lengthening muscles at a constant velocity. We assessed contractile properties by measuring force over shortly interspaced, identical eccentric, and isometric contractions. We then analyzed stretch force, isometric peak force, rate of force development, and relaxation times. Finally, we compared the time courses for the development and cessation of changes in stretch force to known features of postactivation potentiation. In extensor digitorum longus, muscles stretch force consistently increased in a contraction-to-contraction manner by up to 49% [95% confidence interval (CI): 35-64%] whereas isometric peak force simultaneously showed minor declines (8%, 95% CI: 5-10%). The development and cessation of eccentric force potentiation coincided with the development of twitch potentiation and increases in rate of force development. In soleus muscles we found no consistent eccentric potentiation. Characterization of the increase in eccentric force revealed that force only increased in the very beginning of an active stretch. Eccentric force at tetanic activation frequencies potentiates substantially in extensor digitorum longus muscles over consecutive contractions with a time course coinciding with postactivation potentiation. Such eccentric potentiation may be important in sport performance. NEW & NOTEWORTHY Force during eccentric contractions can increase to a magnitude that may have profound consequences for our understanding of skeletal muscle locomotion. This increase in eccentric force occurs over consecutive, shortly interspaced, tetanic contractions in rat extensor digitorum longus muscles--not in rat soleus muscles--and coincides with well-known traits of postactivation potentiation. Eccentric force potentiation may significantly enhance muscle performance in activities involving stretch-shortening cycles. [ABSTRACT FROM AUTHOR]

Disuse muscle atrophy is usually accompanied by changes in skeletal muscle structure, signaling, and contractile potential. Different models of muscle unloading can provide valuable information, but the protocols of experiments with complete immobilization are not physiologically representative of a sedentary lifestyle, which is highly prevalent among humans now. In the current study, we investigated the potential effects of restricted activity on the mechanical characteristics of rat postural (soleus) and locomotor (extensor digitorum longus, EDL) muscles. The restricted-activity rats were kept in small Plexiglas cages (17.0 × 9.6 × 13.0 cm) for 7 and 21 days. After this, soleus and EDL muscles were collected for ex vivo mechanical measurements and biochemical analysis. We demonstrated that while a 21-day movement restriction affected the weight of both muscles, in soleus muscle we observed a greater decrease. The maximum isometric force and passive tension in both muscles also significantly changed after 21 days of movement restriction, along with a decrease in the level of collagen 1 and 3 mRNA expression. Furthermore, the collagen content itself changed only in soleus after 7 and 21 days of movement restriction. With regard to cytoskeletal proteins, in our experiment we observed a significant decrease in telethonin in soleus, and a similar decrease in desmin and telethonin in EDL. We also observed a shift towards fast-type myosin heavy chain expression in soleus, but not in EDL. In summary, in this study we showed that movement restriction leads to profound specific changes in the mechanical properties of fast and slow skeletal muscles. Future studies may include evaluation of signaling mechanisms regulating the synthesis, degradation, and mRNA expression of the extracellular matrix and scaffold proteins of myofibers. [ABSTRACT FROM AUTHOR]

Neuromuscular efficiency is defined as the ratio of work output to stimulation rate. The purpose of these experiments was to test the hypothesis that neuromuscular efficiency would be increased in proportion to posttetanic potentiation, that is, the stimulation‐induced increase in work output displayed by rodent fast‐twitch muscle. To this end, extensor digitorum longus muscles from wild‐type and skeletal myosin light chain kinase knockout (skMLCK−/−) mice were surgically isolated and suspended in vitro (25°C). Concentric force development during shortening at 70% of maximal unloaded shortening velocity was tested at stimulus frequencies between 10 and 80 Hz both before and after a potentiating tetanus. A strong genotype‐dependent difference in the potentiation of concentric work output was observed; concentric work output of wild‐type muscles was increased by 51%–88% while that of skMLCK−/− muscles was increased by only 20%–34% across the frequencies tested. As a result, comparison of work – frequency plots revealed that the frequency required for peak and 50% peak unpotentiated work of wild‐type muscles was decreased from ~80 to 52 Hz and from ~48 to 21 Hz, respectively. By contrast, the frequency required for peak and 50% peak unpotentiated work of skMLCK−/− muscles was decreased from ~80 to 68 Hz and from ~51 to 41 Hz, respectively. Thus, wild‐type muscles with the ability to phosphorylate myosin displayed larger increases in neuromuscular efficiency than skMLCK−/− muscles (25–30 vs 10–15 Hz, respectively). This suggests that the presence of myosin phosphorylation may ameliorate or mitigate fatigue mechanisms associated with high‐frequency stimulation rates. [ABSTRACT FROM AUTHOR]

The negative changes of obesity to the locomotor system are a major concern in the current scenario, where obesity and metabolic syndrome are recurrent in Western societies. A physical exercise is an important tool as a way to rehabilitate obesity, highlighting whole-body vibration, as it is an easy-access modality with few restrictions. In this sense, we sought to evaluate the effect of whole-body vibration on the extensor digitorum longus muscle on a monosodium glutamate-induced obesity model. The main findings of the present study are related to the ability of the treatment with vibration to reduce the obesogenic characteristics and slow down the dyslipidemic condition of the animals. Likewise, the vibration promoted by the vibrating platform was essential in the recovery of the muscle structure, as well as the recovery of the muscle's oxidative capacity, initially compromised by obesity. [ABSTRACT FROM AUTHOR]

Ecccentric muscle contractions are fundamental to everyday life. They occur markedly in jumping, running, and accidents. Following an initial force rise, stretching of a fully activated muscle can result in a phase of decreasing force (“Give”) followed by force redevelopment. However, how the stretch velocity affects “Give” and force redevelopment remains largely unknown. We investigated the force produced by fully activated single-skinned fibers of rat extensor digitorum longus muscles during long stretches. Fibers were pulled from length 0.85 to 1.3 optimal fiber length at a rate of 1%, 10%, and 100% of the estimated maximum shortening velocity. “Give” was absent in slow stretches. Medium and fast stretches yielded a clear “Give.” After the initial force peak, forces decreased by 11.2% and 27.8% relative to the initial peak force before rising again. During the last half of the stretch (from 1.07 to 1.3 optimal fiber length, which is within the range of the expected descending limb of the force-length relationship), the linear force slope tripled from slow to medium stretch and increased further by 60% from medium to fast stretch. These results are compatible with forcible cross-bridge detachment and redevelopment of a cross-bridge distribution, and a viscoelastic titin contribution to fiber force. Accounting for these results can improve muscle models and predictions of multibody simulations. [ABSTRACT FROM AUTHOR]

The main muscles responsible for extension of the toes are the extensor digitorum longus and extensor hallucis longus. Morphological variants of both of these muscles are mostly related to the numbers of tendons and their unusual points of insertion. The case presented shows an accessory band deriving from the extensor digitorum longus and fusing with the extensor hallucis longus, a concomitant additional tendon of the latter inserting to the proximal phalanx of the hallux. Knowledge of these anatomical patterns is important not only from the anatomical but also the clinical point of view and can be useful in lower limb surgery. [ABSTRACT FROM AUTHOR]

Due to urbanization, automation and mechanization of labor, as well as difficult epidemiological situation and self-isolation, the level of daily physical activity in a modern man decreases. The aim of the study was to study the effect of restricted activity on protein synthesis in postural and locomotor muscles. An experiment with activity restricted for 21 days was carried out on Wistar rats. The intensity of protein synthesis and anabolic signaling pathways was studied in the soleus muscle (m. soleus) mainly consisting of slow fibers, and the extensor digitorum longus muscle (m. EDL), mainly consisting of fast fibers. The mass of m. soleus and m. EDL was reduced, while a significant decrease in protein synthesis was observed only in m. EDL. There was also a decrease in the phosphorylation of S6 ribosomal protein only in the fast muscle. At the same time, in contrast to m. EDL, а GSK3β phosphorylation was decreased in m. soleus. Additionally, the markers of proteolysis were studied. In the experiment, a decrease in the expression of MuRF-1 in m. soleus and Atrogin-1/MAFbx in m. EDL was observed, as well as an increase in the expression of calpains in m. soleus. Thus, atrophic processes caused by restricted activity in fast and slow muscles are determined by different signaling mechanisms. [ABSTRACT FROM AUTHOR]

Endocannabinoids (ECs) mediate effects via cannabinoid receptor types 1 and 2 (CB1 and 2) and transient receptor potential channel-vanilloid subfamily member 1 (TRPV1) channels. In high-fat diet (HFD)-induced obese mice overactivity of the EC system and inhibition of CB1 increase skeletal muscle glucose uptake. We explored the role of TRPV1. Male TRPV1-/-(WT) and TRPV1-/-(KO)-mice were fed (20 wk) a standard laboratory diet (SLD) or HFD. An intraperitoneal glucose tolerance test was performed. RT-PCR was performed to measure mRNA of genes involved in glucose/lipid metabolism and the EC system in soleus (SOL) and extensor digitorum longus (EDL) muscles. Cultured L6 cells were used to measure glucose uptake in skeletal muscle. HFD mice weighed more and had higher insulin levels than SLD mice, with no genotype differences. Basal and peak glucose were higher in HFD mice irrespective of genotype, but glucose cleared faster in HFD WT vs. HFD KO-mice. 2-Arachidonoylglycerol augmented insulin-induced glucose uptake in skeletal L6-cells, an effect blocked by the TRPV1 antagonist SB-366791. In EDL, fatty acid amide hydrolase (FAAH) mRNA was increased in KO vs. WT mice, irrespective of diet. Pyruvate dehydrogenase kinase isozyme 4 (PDK4) and mitochondrial uncoupling protein 3 (UCP3) were elevated and FA desaturase 2 (FADS2) mRNA lower in HFD mice, irrespective of genotype. CB1 and stearoyl-CoA desaturase 1 (SCD1) were lower in HFD WT mice only. In SOL, PDK4, UCP3, hormone-sensitive lipase (LIPE), fatty acid translocase (CD36), and carnitine palmitoyl transferase 2 (CPT2) were elevated and SCD1, FAAH, FADS2, and Troponin 1 (TNNC1) mRNA lower in HFD mice, irrespective of genotype. In conclusion, TRPV1 regulates glucose disposal in HFD mice. We propose that TRPV1 plays a role in coordinating glucose metabolism in EDL under conditions of metabolic stress. [ABSTRACT FROM AUTHOR]

Copyright of Acta Scientiarum: Health Sciences is the property of Universidade Estadual de Maringa and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The aim of this study was to compare the effects of adenosine-5'-triphosphate (ATP) and adenosine on the contractility of rodent extensor digitorum longus (EDL) muscle at normal and low temperatures.Methods: Contractions of rat and mouse isolated EDL were induced by either electrical stimulation (ES) or exogenous carbachol and recorded in the presence of ATP or adenosine (both at 100 μM).Results: ATP at all temperatures caused a decrease of the contractions induced by carbachol in rat and mouse EDL and ES-induced contractions in rat EDL, while it potentiated the ES-induced contractions of mouse EDL. Adenosine reduced the contractility of rat and mouse EDL evoked by ES and did not affect the carbachol-induced contractions of rat and mouse EDL at any temperature.Discussion: Under various temperature conditions, ATP inhibits pre- but potentiates postsynaptic processes in the mouse EDL; in the rat EDL ATP causes only inhibition of neuromuscular conduction. Muscle Nerve 59:509-516, 2019. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The effects of dehydration on muscle performance in human are still contradictory, notably regarding muscle force. The effect of water deprivation (WD) on mechanical properties of skeletal muscle, and more precisely its impact on slow and fast muscles, remains largely unknown. The aim of this study was to determine for the first time whether WD leads to changes in contractile properties of skeletal muscle and whether these changes were muscle‐type‐specific. Methods: Sixteen‐week‐old male rats were assigned to either a control group (C) with water or a 96‐hour WD group. At the end of the period, twitch and tetanus properties, as well as biochemical and structural analysis, were performed on soleus (SOL) and extensor digitorum longus (EDL) muscles. Results: Absolute twitch (Pt) and tetanic (P0) tension were, respectively, 17% and 14% lower in EDL of WD rats as compared with C rats, whereas unexpected increases of 43% and 25% were observed in SOL. Tensions normalized with respect to muscle mass were not affected by WD in EDL, whereas they were increased by more than 40% in SOL. A 96‐hour WD period leads to a decrease in fibre cross‐sectional area and absolute myofibrillar content only in EDL. Conclusion: It is hypothesized that differences in the results between slow and fast muscles may come from (i) a muscle‐type‐specific effect of WD on protein balance, EDL showing a greater myofibrillar protein breakdown and (ii) a greater sensitivity to osmolality changes induced by WD in EDL than in SOL. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: Atorvastatin is usually used to decrease the amount of fatty substances in individuals with type 2 diabetes mellitus. However, it can cause side‐effects, such as breakdown of skeletal muscle tissue. The present study focused on the effects of atorvastatin on autophagy of the skeletal muscles in diabetic rats. Materials and Methods: Diabetes in rats in the diabetic (D) and atorvastatin (T) groups was induced using streptozotocin (65 mg/kg, intraperitoneal injection). Next, rats in the T group were treated with atorvastatin (10 mg/kg/day, intragastric administration), whereas rats in the control and D groups were given water. Additionally, the rats in T and D groups were fed a high‐fat and high‐sugar diet for 10 weeks. Subsequently, the histopathological changes, and expression levels of microtubule‐associated protein 1 light chain 3 (LC3)‐I/‐II and p62 in the skeletal muscle specimens in the three groups were analyzed. Results: Rats in the T group had reduced lipid droplets, cholesterol and low‐density lipoprotein (P < 0.05) levels than those in the D group. Disordered atrophic myocytes, incrassated vascular walls and decreased cross‐sectional area of type I fibers were found using hematoxylin–eosin and adenosine triphosphatase staining in the D and T groups. The messenger ribonucleic acid and protein levels of LC3‐II and the LC3‐II/LC3‐I ratio were increased in the T group compared with those in the other groups (P < 0.05), whereas the protein level of p62 showed the opposite trend. Conclusions: Atorvastatin enhanced the autophagy level of skeletal muscles to decrease lipid deposition, which possibly exacerbated myopathy. [ABSTRACT FROM AUTHOR]

The distribution of Na/K-ATPase α-isoforms in skeletal muscle is unique, with α1 as the minor (15%) isoform and α2 comprising the bulk of the Na/K-ATPase pool. The acute and isoform-specific role of α2 in muscle performance and resistance to fatigue is well known, but the isoform-specific role of α1 has not been as thoroughly investigated. In vitro, we reported that α1 has a role in promoting cell growth that is not supported by α2. To assess whether α1 serves this isoform-specific trophic role in the skeletal muscle, we used Na/K-ATPase α1-haploinsufficient (α1+/−) mice. A 30% decrease of Na/K-ATPase α1 protein expression without change in α2 induced a modest yet significant decrease of 10% weight in the oxidative soleus muscle. In contrast, the mixed plantaris and glycolytic extensor digitorum longus weights were not significantly affected, likely because of their very low expression level of α1 compared with the soleus. The soleus mass reduction occurred without change in total Na/K-ATPase activity or glycogen metabolism. Serum analytes including K+, fat tissue mass, and exercise capacity were not altered in α1+/− mice. The impact of α1 content on soleus muscle mass is consistent with a Na/K-ATPase α1-specific role in skeletal muscle growth that cannot be fulfilled by α2. The preserved running capacity in α1+/− is in sharp contrast with previously reported consequences of genetic manipulation of α2. Taken together, these results lend further support to the concept of distinct isoform-specific functions of Na/K-ATPase α1 and α2 in skeletal muscle. [ABSTRACT FROM AUTHOR]

Objective: The importance of skeletal muscle as the largest metabolic tissue in diabetes remains more unknown than other metabolic tissues of the body. The purpose of this study was to evaluate the effects of six weeks endurance training on the soleus and extensor digitorum longus (EDL) myonuclear number in diabetic male wistar rats. Materials and Methods: In this study, 40 male wistar rats about 10 weeks old and weighing 200-250 grams allocated randomly in four groups of diabetic training (DT), diabetic control (DC), healthy training (HT) and healthy control (HC). For induction of diabetes, DT and DC groups were intraperitoneally injected by streptozotocin (STZ), and the training groups performed incremental endurance training on the treadmill for six weeks. Fourty eight hours after the last training session, all rats were killed and tissue samples of soleus and EDL muscles were removed and fixed in 10% buffered formalin. The sections were prepared with six µm thickness and stained with hematoxylin-eosin. The myonuclear numbers were counted in prepared plates by randomly style at the ten field microscopy. Data analysis was done with One-way and two-way ANOVA and Tukey's post hoc test. Results: Our findings showed that myonuclear number in diabetic groups was lower in both soleous and EDL muscles (P-value: 0.0001). furtheremore in DT and HT groups, the number of nuclei increased significantly (P-value: 0.0001). Conclusion: Endurance physical activities as a non-medicinal strategy can play an important role in maintenance of the structure and the function of skeletal muscles and thereby improving the quality of life in diabetes. [ABSTRACT FROM AUTHOR]

Microcomputed tomography (µCT) is an imaging technology to assess bone microarchitecture, a determinant of bone strength. When measured in vivo, µCT exposes the skeletal site of interest to a dose of radiation, in addition to nearby skeletal muscles as well. Therefore, the aim of this study was to determine the effects of repeated radiation exposure from in vivo µCT on muscle health - specifically, muscle morphometrics, contractile function, and enzyme activity. This study exposed the right hind limb of female mice to either a low (26 cGy) or moderate (46 cGy) dose, at 2, 4, and 6 months of age, while the left hind limb of the same animal was exposed to a single dose at 6 months to serve as a nonirradiated control. Muscle weight, cross-sectional area, isometric contractile function, and representative maximal enzyme activities of amino acid, fatty acid, glucose, and oxidative metabolism in extensor digitorum longus (EDL) and soleus were assessed. Low-dose radiation had no effect. In contrast, moderate-dose radiation resulted in a 5% increase in time-to-peak tension and 16% increase in half-relaxation time of isometric twitches in EDL, although these changes were not seen when normalized to force. Moderatedose radiation also resulted in an ~33% decrease in citrate synthase activity in soleus but not EDL, with no changes to the other enzymes measured. Thus, three low doses of radiation over 6 months had no effect on contractile function or metabolic enzyme activity in soleus and EDL of female mice. In contrast, three moderate doses of radiation over 6 months induced some effects on metabolic enzyme activity in soleus but not EDL. Future studies that wish to investigate muscle tissue that is adjacent to scanned bone should take radiation exposure dose into consideration. [ABSTRACT FROM AUTHOR]

The skeletal myosin light chain kinase (skMLCK) catalyzed phosphorylation of the myosin regulatory light chain (RLC) is associated with potentiation of force, work, and power in rodent fast twitch muscle. The purpose of this study was to compare concentric responses of EDL from wild-type (WT) and skMLCK devoid (skMLCK) muscles at a range of shortening speeds (0.05 to 0.70 V ) around that expected to produce maximal power (in vitro, 25 °C) both before (unpotentiated) and after (potentiated) a potentiating stimulus (PS). When collapsed across all speeds tested, neither unpotentiated force, work, or power differed between genotypes (all data n = 10, P < 0.05). In contrast, although both genotypes displayed speed-dependent increases, these increases were greater for WT than skMLCK muscles. For example, when collapsed across the six fastest speeds we tested, both concentric force and power were increased 30-34 % in WT but only 15-17 % in skMLCK muscles. In contrast, at the two slowest speeds, these parameters were increased in WT but decreased in skMLCK muscles (8-10 and 7-9 %, respectively). Intriguingly, potentiation of concentric force and power was optimal near speeds producing maximal power in both genotypes. Because the PS elevated RLC phosphorylation above resting levels in WT but not in skMLCK muscles, our data suggest that skMLCK-catalyzed phosphorylation of the RLC is required for maximal concentric power output of mouse EDL muscle stimulated at high frequency in vitro. [ABSTRACT FROM AUTHOR]

Background and Objective: Endurance activity affects muscle gene expression leading to the improvement of its function and effectiveness. Meanwhile, PGC-1 alpha transcription factor increases mitochondrial biogenesis in skeletal muscles. This study was designed to investigate the effect of an endurance activity program on pgc-1 alpha expression gene of fast and slow twitch muscles. Materials and Methods: 14 male wistar rats weighing 113±20 grams under controlled conditions were housed after familiarization (231±24 grams) and then were randomly assigned to control (n=7) and treatment (n=7) groups. The treatment group performed an endurance activity program (30 m/min, 50 min, and 6 sessions per week for 14-weeks) on a motorized treadmill. 48 hours after the end of the last session, the rats in both groups were anesthetized and sacrificed and the soleus and extensor digitorum longus muscles were removed. Real time RT-PCR was used to determine expression levels of pgc-1 alpha gene. T-test was used to compare the results. Results: 14 weeks of endurance activity increased pgc-1 alpha gene expression in extensor digitorum longus and soleus muscles. The rate of this gene expression in soleus muscle of treatment group was significantly higher (P=0.0001) in comparison to the control group and also in the treatment group extensor digitorum longus muscle was significantly more (P=0.006) than the control group. Conclusion: Though endurance activity has similar effect on slow and fast twitch pgc-1 alpha gene expression, it seems that the intensity of this effect is higher in slow twitch muscle. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Zoology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Skeletal muscle fibers are mainly categorized into red and white fiber types, and the ratio of red/white fibers within muscle mass plays a crucial role in meat quality such as tenderness and flavor. To better understand the molecular difference between the two muscle fibers, this study takes advantage of RNA-seq to compare differences in the transcriptome between extensor digitorum longus (EDL; white fiber) and soleus (Sol; red fiber) muscles of large white pigs. In total, 89,658,562 and 46,723,568 raw reads from EDL and Sol were generated, respectively. Comparison between the two transcriptomes revealed 561 differentially expressed genes, with 408 displaying higher and 153 lower levels of expression in Sol. Quantitative real-time polymerase chain reaction validated the differential expression of nine genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis discovered several differentially enriched biological functions and processes of the two muscles. Moreover, transcriptome comparison between EDL and Sol identified many muscle-related genes (CSRP3, ACTN2, MYL1, and MYH6) and pathways related to myofiber formation, such as focal adhesion, tight junction formation, extracellular matrix (ECM)-receptor pathway, calcium signaling, and Wnt signaling. In addition, 58,362 and 58,359 single nucleotide polymorphisms were identified in EDL and Sol, respectively, and the sequence of 9069 genes was refined at the 5′, 3′ or both ends. Numerous novel transcripts and alternatively spliced RNAs were also identified. Our transcriptome analysis constitutes valuable sequence resource for uncovering important genes and pathways involved in muscle fiber type determination, and might help further our understanding of the molecular mechanisms in different types of muscle. [ABSTRACT FROM AUTHOR]

Copyright of Schweizerische Zeitschrift für Sportmedizin & Sporttraumatologie is the property of Schwiez Zschr Sportmed Sporttraumatologie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Unlabelled: Synovial chondromatosis is a rare pathology in the foot and ankle region. We present a case of concomitant tenosynovial chondromatosis of the extensor digitorum longus tendon and synovial chondromatosis of the ankle, which was successfully treated by extensor digitorum tendon tendoscopy and ankle arthroscopy.Levels Of Evidence: Therapeutic, Level IV: Case study. [ABSTRACT FROM AUTHOR]

The primary deficiency in the membrane cytoskeletal protein dystrophin results in complex changes in dystrophic muscles. In order to compare the degree of secondary alterations in differently affected subtypes of skeletal muscles, we have conducted a global analysis of proteome-wide changes in various dystrophin-deficient muscles. In contrast to the highly degenerative mdx diaphragm muscle, which showed considerable alterations in 35 distinct proteins, the spectrum of mildly to moderately dystrophic skeletal muscles, including interosseus, flexor digitorum brevis, soleus, and extensor digitorum longus muscle, exhibited a smaller number of changed proteins. Compensatory mechanisms and/or cellular variances may be responsible for differing secondary changes in individual mdx muscles. Label-free mass spectrometry established altered expression levels for diaphragm proteins associated with contraction, energy metabolism, the cytoskeleton, the extracellular matrix and the cellular stress response. Comparative immunoblotting verified the differences in the degree of secondary changes in dystrophin-deficient muscles and showed that the up-regulation of molecular chaperones, the compensatory increase in proteins of the intermediate filaments, the fibrosis-related increase in collagen levels and the pathophysiological decrease in calcium binding proteins is more pronounced in mdx diaphragm as compared to the less severely affected mdx leg muscles. Annexin, lamin, and vimentin were identified as universal dystrophic markers. [ABSTRACT FROM AUTHOR]

Myostatin is an important negative regulator of skeletal muscle growth. The hypermuscular Compact (Cmpt) mice carry a 12-bp natural mutation in the myostatin propeptide, with additional modifier genes being responsible for the phenotype. Muscle cellularity of the fast-type tibialis anterior (TA) and extensor digitorum longus (EDL) as well as the mixed-type soleus (SOL) muscles of Cmpt and wild-type mice was examined by immunohistochemical staining of the myosin heavy chain (MHC) proteins. In addition, transcript levels of MHC isoforms were quantified by qPCR. Based on our results, all investigated muscles of Cmpt mice were significantly larger compared with that of wild-type mice, as characterized by fiber hyperplasia of different grades. Fiber hypertrophy was not present in TA; however, EDL muscles showed specific IIB fiber hypertrophy while the (I and IIA) fibers of SOL muscles were generally hypertrophied. Both the fast TA and EDL muscles of Cmpt mice contained significantly more glycolytic IIB fibers accompanied by a decreased number of IIX and IIA fibers; however, this was not the case for SOL muscles. In summary, despite the variances found in muscle cellularity between the different myostatin mutant mice, similar glycolytic shifts were observed in Cmpt fast muscles as in muscles from myostatin knockout mice. [ABSTRACT FROM PUBLISHER]

IL-6 is an exercise-regulated myokine that has been suggested to increase lipolysis in fast-twitch skeletal muscle. However, it is not known if a similar effect is present in slow-twitch muscle. Furthermore, epinephrine increases IL-6 secretion from skeletal muscle, suggesting that IL-6 could play a role in mediating the lipolytic effects of catecholamines. The purpose of this study was to determine whether IL-6 stimulates skeletal muscle lipolysis in a fiber type dependent manner and is required for epinephrine-stimulated lipolysis in murine skeletal muscle. Soleus and extensor digitorum longus (EDL) muscles from male C57BL/6J wild-type and IL-6-/- mice were incubated with 1 μM (183 ng/ml) epinephrine or 75 ng/ml recombinant IL-6 (rIL-6) for 60 min. IL-6 treatment increased 5=-AMP-activated protein kinase and signal transducer and activator of transcription 3 phosphorylation and glycerol release in isolated EDL but not soleus muscles from C57BL/6J mice. Conversely, epinephrine increased glycerol release in soleus but not EDL muscles from C57BL/6J mice. Basal lipolysis was elevated in soleus muscle from IL-6-/- mice, and this was associated with increases in adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58). The increase in ATGL content does not appear to be due to a loss of IL-6's direct effects, because ex vivo treatment with IL-6 failed to alter the expression of ATGL mRNA in soleus muscle. In summary, IL-6 stimulates lipolysis in glycolytic but not oxidative muscle, whereas the opposite fiber type effect is seen with epinephrine. The absence of IL-6 indirectly upregulates lipolysis, and this is associated with increases in ATGL and its coactivator CGI-58. [ABSTRACT FROM AUTHOR]

X-linked muscular dystrophy of the mouse ( mdx) has been reported to progressively remodel skeletal muscle to preferentially reduce fast fiber composition. Despite this, mdx muscle displays normal levels of posttetanic potentiation (PTP). Since PTP may primarily depend on phosphorylation of the myosin regulatory light chain (RLC) in fast muscle fibers, maintenance of PTP with mdx disease progression is paradoxical and may represent an adaptation of the diseased muscle. This study assesses the role of RLC phosphorylation during PTP of mdx muscle. Extensor digitorum longus muscles were isolated from mdx and from C57BL/10 (control) mice at ~50 (young) and ~300 (adult) days and stimulated in vitro (25°C) to induce PTP. During potentiation, muscles were harvested for subsequent determination of RLC phosphorylation levels. Immunofluorescence was used to assess muscle fiber type composition and no age effects were found. The magnitude of PTP was higher ( P < 0.05) in mdx than control muscles at both young ( mdx: 21.9 ± 1.6%; control: 17.7 ± 1.2%) and adult ( mdx: 30.4 ± 1.8%; control: 23.2 ± 2.2%) ages. However, RLC phosphate content was similar between all groups both at rest and following stimulation. Our results are consistent with a model where the sensitivity of mdx muscle to RLC phosphorylation-induced force potentiation is increased by disease- and age-dependent alterations in excitation-contraction coupling noted for mdx and aging muscle. [ABSTRACT FROM AUTHOR]

Yamada T, Zhang SJ, Westerblad H, Katz A. β-Hydroxybutyrate inhibits insulin-mediated glucose transport in mouse oxidative muscle. Am J Physiol Endocrinol Metab 299: E364-E373, 2010. First published June 1, 2010; doi:10.1152/ajpendo.00142.2010.--Blood ketone body levels increase during starvation and untreated diabetes. Here we tested the hypothesis that ketone bodies directly inhibit insulin action in skeletal muscle. We investigated the effect of D,L-β-hydroxybutyrate (BOH; the major ketone body in vivo) on insulin-mediated glucose uptake (2-deoxyglucose) in isolated mouse soleus (oxidative) and extensor digitorum longus (EDL; glycolytic) muscle. BOH inhibited insulin-mediated glucose uptake in soleus (but not in EDL) muscle in a time- and concentration-dependent manner. Following 19.5 h of exposure to 5 mM BOH, insulin-mediated (20 mU/ml) glucose uptake was inhibited by ∼90% (substantial inhibition was also observed in 3-O-methylglucose transport). The inhibitory effect of BOH was reproduced with D- but not L-BOH. BOH did not significantly affect hypoxia- or AICAR-mediated (activates AMP-dependent protein kinase) glucose uptake. The BOH effect did not require the presence/utilization of glucose since it was also seen when glucose in the medium was substituted with pyruvate. To determine whether the BOH effect was mediated by oxidative stress, an exogenous antioxidant (1 mM tempol) was used; however, tempol did not reverse the BOH effect on insulin action. BOH did not alter the levels of total tissue GLUT4 protein or insulin-mediated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 but blocked insulin-mediated phosphorylation of protein kinase B by ∼50%. These data demonstrate that BOH inhibits insulin-mediated glucose transport in oxidative muscle by inhibiting insulin signaling. Thus ketone bodies may be potent diabetogenic agents in vivo. [ABSTRACT FROM AUTHOR]

There is consensus about whether making muscles abnormally large by reducing myostatin activity affects force-generating capacity or the ability to perform activities requiring muscular endurance. We therefore examined grip force, contractile properties of extensor digitorulongus (EDL) muscles, and voluntary wheel running in mice in which myostatin was depleted after normal muscle development. Cre recombinase activity was induced to knock out exon 3 of the myostatin genein 4-mo-old mice in which this exon was flanked by loxP sequences (Mstn[f/f]). Control mice with normal myostatin genes (Mstn[w/w received the same Cre-activating treatment. Myostatin depletion increased the mass of all muscles that were examined (gastrocnemius quadriceps, tibialis anterior, EDL, soleus, triceps) by ~20-40%. Grip force, measured multiple times 2-22 wk after myostatin knockout was not consistently greater in the myostatin-deficient mice. EDL contractile properties were determined 7-13 mo after myostatin knockout. Twitch force tended to be greater in myostatin-deficiency muscles (+24%; P = 0.09), whereas tetanic force was not consistently elevated (mean + 11%; P = 0.36), even though EDL mass was greater than normal in all myostatin-deficient mice (mean +36%; P< 0.001). The force deficit induced by eccentric contractions was approximately twofold greater in myostatin-deficient than in norma EDL muscles (31% vs. 16% after five eccentric contractions; P = 0.02). Myostatin-deficient mice ran 19% less distance (P < 0.01) the control mice during the 12 wk following myostatin depletion, primarily because of fewer running bouts per night rather than diminished running speed or bout duration. Reduced specific tension (ratio of force to mass) and reduced running have been observed after muscle hypertrophy was induced by other means, suggesting that they are characteristics generally associated with abnormally large muscles rather than unique effects of myostatin deficiency. [ABSTRACT FROM AUTHOR]

Electroporation is a technique used in vitro, ex vivo, and in vivo to permeabilize cell membranes. The effect on the tissue describes a continuum ranging from mild perturbations to massive tissue damage. Thus care should be taken when choosing pulses for a given application. Here the effects of electroporation paradigms ranging from severe to very gentle permeabilization were investigated on soleus, mainly com- posed of slow-twitch fibers, and extensor digitorum longus (EDL) and tibialis anterior (TA), almost exclusively composed of fast-twitch fibers. Five key physiological parameters were studied: force, muscle Na+, K+, and Ca2+ content, and plasma lactate dehydrogenase activity. Four-week-old Wistar rats were anesthetized, and the lower part of the hind leg was electroporated. Blood samples were collected from the tail vein, and at the times indicated animals were killed and TA, EDL, and soleus muscles were collected for analysis of force and ion contents. Muscles were given eight high-voltage pulses of 100-μs duration (8HV) at varying field intensity, one short high-voltage pulse combined with one long low-voltage pulse (HVLV), or eight medium-voltage pulses of 20-ms duration (8MV). Intensity of the electrical field strength was determinant for the degree of changes observed in the muscle. Field strengths below 300 V/cm did not give rise to measurable changes, whereas 8HV pulses at high field intensities (1,200 V/cm) caused severe and long-lasting damage to the muscle. Interestingly, the damage was more pronounced in EDL and TA compared with soleus, possibly because of the difference in fiber type composition. HVLV only caused temporary changes, with force and ion content being normalized by 4 h, suggesting that this pulse combination may be useful for the introduction of ions and molecules (e.g., DNA) into muscle cells. [ABSTRACT FROM AUTHOR]

5'-AMP-activated protein kinase (AMPK) regulates several aspects of metabolism. Recently, A-769662 was shown to activate AMPK in skeletal muscle. However, no biological effects of AMPK activation by A-769662 in this tissue have been reported. We hypothesized that A-769662 would increase glucose uptake in skeletal muscle. We studied incubated soleus and extensor digitorum longus (EDL) muscles from 129S6/sv and C57BL/6 mice. Glucose uptake increased only in soleus from I 29S6/sv when concentrations of A-769662 were 500 μM (∼15%, P < 0.05) and 1 mM (∼60%, P < 0.01). AMPK β1but not β2-containing complexes were dose dependently activated by A-769662 in muscles from both genotypes (∼100% at 200 μM and 300-600% at 1 mM). The discrepancy between the A-769662induced AMPK activation pattern and stimulation of glucose uptake suggested that these effects were unrelated. A-769662 increased phosphorylation of Akt in both muscles from both genotypes, with phosphorylation of T308 being significantly higher in soleus than in EDL in 129S6/sv mice (P < 0.01). In soleus from 129S6/sv mice, insulin receptor substrate 1-associated phosphatidylinositol 3 (PI3)kinase activity was markedly increased with A-769662, and Akt phosphorylation and glucose uptake were inhibited by wortmannin while phosphorylation of acetyl-CoA carboxylase (S227) was unaffected. Thus, A-769662 activates β1-containing AMPK complexes in skeletal muscle but induces glucose uptake through a PI3-kinase-dependent pathway. Although development of A-769662 has constituted a step forward in the search for AMPK activators targeting specific AMPK trimers, our data suggest that in intact muscle, A-769662 has off-target effects. This may limit use of A-769662 to study the role of AMPK in skeletal muscle metabolism. [ABSTRACT FROM AUTHOR]

Martin PT, Xu R, Rodino-Klapac LR, Oglesbay E, Camboni M, Montgomery CL, Shontz K, Chicoine LG, Clark KR, Sahenk Z, Mendell JR, Janssen PM. Overexpression of Galgt2 in skeletal muscle prevents injury resulting from eccentric contractions in both mdx and wild-type mice. Am J Physiol Cell Physiol 296: C476-C488, 2009. First published December 24, 2008; doi: 10.1 152/ajpcell.00456.2008.-The cytotoxic T cell (CT) Ga1NAc transferase, or Galgt2, is a UDPGa1NAc:β1,4-N-acetylgalactosaminyltransferase that is localized to the neuromuscular synapse in adult skeletal muscle, where it creates the synaptic CT carbohydrate antigen (Ga1NAcβ1,4[NeuAc(orGc)a2, 3]Galβ1 ,4GlcNAcβ). Overexpression of Galgt2 in the skeletal muscles of transgenic mice inhibits the development of muscular dystrophy in mdx mice, a model for Duchenne muscular dystrophy. Here, we provide physiological evidence as to how Galgt2 may inhibit the development of muscle pathology in mdx animals. Both Galgt2 transgenic wild-type and mdx skeletal muscles showed a marked improvement in normalized isometric force during repetitive eccentric contractions relative to nontransgenic littermates, even using a paradigm where nontransgenic muscles had force reductions of 95% or more. Muscles from Galgt2 transgenic mice, however, showed a significant decrement in normalized specific force and in hindlimb and forelimb grip strength at some ages. Overexpression of Galgt2 in muscles of young adult mdx mice, where Galgt2 has no effect on muscle size, also caused a significant decrease in force drop during eccentric contractions and increased normalized specific force. A comparison of Galgt2 and microdystrophin overexpression using a therapeutically relevant intravascular gene delivery protocol showed Galgt2 was as effective as microdystrophin at preventing loss of force during eccentric contractions. These experiments provide a mechanism to explain why Galgt2 overexpression inhibits muscular dystrophy in mdx muscles. That overexpression also prevents loss of force in nondystrophic muscles suggests that Galgt2 is a therapeutic target with broad potential applications. [ABSTRACT FROM AUTHOR]

The actin-binding protein α-actinin-3 is one of the two isoforms of α-actinin that are found in the Z-discs of skeletal muscle. α-Actinin-3 is exclusively expressed in fast glycolytic muscle fibers. Homozygosity for a common polymorphism in the ACTN3 gene results in complete deficiency of α-actinin-3 in about 1 billion individuals worldwide. Recent genetic studies suggest that the absence of α-actinin-3 is detrimental to sprint and power performance in elite athletes and in the general population. In contrast, α-actinin-3 deficiency appears to be beneficial for endurance athletes. To determine the effect of α-actinin-3 deficiency on the contractile properties of skeletal muscle, we studied isolated extensor digitorum longus (fast-twitch) muscles from a specially developed α-actinin-3 knockout (KO) mouse. α-Actinin-3-deficient muscles showed similar levels of damage to wild-type (WT) muscles following lengthening contractions of 20% strain, suggesting that the presence or absence of α-actinin-3 does not significantly influence the mechanical stability of the sarcomere in the mouse. α-Actinin-3 deficiency does not result in any change in myosin heavy chain expression. However, compared with α-actinin-3-positive muscles, α-actinin-3-deficient muscles displayed longer twitch half-relaxation times, better recovery from fatigue, smaller cross-sectional areas, and lower twitch-to-tetanus ratios. We conclude that α-actinin-3 deficiency results in fast-twitch, glycolytic fibers developing slower-twitch, more oxidative properties. These changes in the contractile properties of fast-twitch skeletal muscle from α-actinin-3-deficient individuals would be detrimental to optimal sprint and power performance, but beneficial for endurance performance. [ABSTRACT FROM AUTHOR]

Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow recording of muscle contractile properties of tongue and extensor digitorum longus (EDL) muscle in the hindlimb. In the same animals, the following measurements were made: (a) twitch contraction time (CT; in milliseconds), (b) half decay time (HDT; in milliseconds), (c) maximum twitch force (in grams), (d) tetanic force, and (e) fatigue index determined from repetitive stimulation of the muscles. Results: No significant differences were observed in young versus old groups in retrusive tongue forces, whereas a significant (p < .05) decrement in EDL tetanic forces was found in old rats. Slower CT in old rats was observed only in the tongue. Old and young groups were not significantly different in fatigue index or HDT for tongue or EDL. Conclusions: Old animals generated equivalent maximum tongue forces with stimulation, but they were slower in achieving these forces than young animals. Limb and cranial muscles were not affected equally by aging. As such, information derived from limb muscle studies may not easily generalize to the cranial motor system. [ABSTRACT FROM AUTHOR]

The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic group of motoneurones that innervates the bulbocavernosus (BC) and levator ani (LA), skeletal muscles that attach to the base of the penis. In many species, including mice, rats and hamsters, the LA and BC have been found to be highly responsive to androgen and, in rats, these muscles mediate several effects of androgen on the SNB system. However, characterising the SNB system in mice is important because of the availability of genetic models in this species. In the present study, we examined AR expression in skeletal muscles of C57/BlJ6 adult male mice using immunoblotting and immunocytochemistry, comparing the BC/LA to the androgen-unresponsive extensor digitorum longus (EDL). We found similar differences in AR expression for these muscles in the mouse as previously reported for rats. In mice, the BC/LA contains more AR protein than does the EDL. At the cellular level, the LA contains a higher percentage of AR positive myonuclei and fibroblasts than does the EDL. Finally, AR expression is enriched at the neuromuscular junction of mouse LA fibres. The increased expression of AR in the LA compared to the EDL in both muscle fibres and fibroblasts indicates that each cell type may critically mediate androgen action on the SNB system in mice. [ABSTRACT FROM AUTHOR]

Purpose: Prolonged denervation of skeletal muscles results in atrophy and poor recovery of motor function following delayed reinnervation. Electrical stimulation reduces denervation atrophy. We hypothesized that electrical stimulation of denervated extensor digitorum longus (EDL) muscles during a prolonged period between nerve axotomy and opportunity for reinnervation by motoneurons after nerve-repair would enhance the recovery of muscle mass, force and motor-function. Methods: The EDL muscles of rats were denervated for 3.5 months by peroneal nerve axotomy, then repaired with an end-to-end neurorrhaphy, and allowed to recover for 6.5 months. During the period of denervation, some of the rats received a protocol of electrical stimulation that had previously been shown to dramatically attenuate the effects of denervation atrophy through 4 months. Other experimental groups included unoperated control muscles, denervated muscles, and axotomy followed immediately by nerve-repair. Final evaluations included walking track analysis, maximum force measured in situ by indirect stimulation of the nerve, and muscle mass. Results: The hypothesis was not supported. Electrical stimulation during the period of denervation did not enhance recovery of muscle mass, force or motor function. Conclusion: The primary factors that inhibited reinnervation and recovery following delayed reinnervation were not alleviated by the electrical stimulation during the period of muscle denervation. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effects of peripheral arterial insufficiency, exercise, and vitamin C administration on muscle performance, cross-sectional area, and ultrastructural morphology in extensor digitorum longus (EDL) and soleus (Sol) muscles in rats. Adult Wistar rats were assigned to ischemia alone (isch), ischemia-exercised (exe), ischemia-vitamin C (vit C), and ischemia-exercise-vitamin C (vit C + exe) groups. Ischemia was achieved via unilateral ligation of the right common iliac artery. Contralateral muscles within the same animal served as controls. Exercise protocol consisted of 50-min intermittent level running performed every other day for 5 days. Vitamin C (100 mg/kg body wt) was administered intraperitoneally on a daily basis throughout the 14 days of the experiment. With regard to the EDL muscle, ischemia alone reduced muscle strength, which was not recovered after vitamin C administration. Exercise alone following ischemia induced the most severe structural damage and cross-sectional area decrease in the muscle, yet the reduction in tetanic tension was not significant. Exercise in conjunction with vitamin C administration preserved ischemia-induced EDL muscle tetanic tension. In the Sol muscle, a significant reduction in single twitch tension after vitamin C administration was found, whereas the tetanic force of the ischemic Sol was not significantly decreased compared with the contralateral muscles in any group. Ischemic Sol muscle cross-sectional area was reduced in all but the exe groups. In Sol, muscle strength was reduced in the vit C group, and mean cross-sectional area of ischemic Sol muscles was reduced in all groups except the exe group. These results illustrate that mild exercise, combined with a low dose of vitamin C supplementation, may have beneficial effects on ischemic EDL muscle with a smaller effect on the Sol muscle. [ABSTRACT FROM AUTHOR]

The K+ channel blocker 3,4-diaminopyrindine (DAP) increases diaphragm force, use of which could potentially improve muscle performance during functional neuromuscular stimulation. To determine the extent of hindlimb muscle force augmentation, and delineate whether DAP effects vary in muscles comprised of mainly slow versus fast fibers, rat soleus, extensor digitorum longus (EDL) and diaphragm muscle samples were studied in vitro. DAP increased force of all three muscles, but at high concentrations the force increases were transient and were followed by declines in force below baseline. The maximum DAP-induced twitch force increase was smaller for soleus (38 ± 7%) than both EDL (94 ± 12%) (P < 0.05) and diaphragm (93 ± 13%) (P < 0.01). During fatigue-inducing 20 Hz stimulation (tested at an intermediate DAP concentration), force of soleus muscle remained significantly elevated by DAP for the entire testing period, force of DAP-treated EDL muscle rapidly declined to values in untreated muscle, and force of DAP-treated diaphragm had an intermediate force-time profile. Muscles varied in extent to which isometric contractile kinetics were altered by DAP. Thus, the K+ channel blocker DAP improves contractile performance of limb muscles, but the profile of improvement is distinct between the soleus and EDL muscles. [ABSTRACT FROM AUTHOR]

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Striated muscle contraction is powered by actin-activated myosin ATPase. This process is regulated by Ca2+ via the troponin complex. Slow- and fast-twitch fibers of vertebrate skeletal muscle express type I and type II myosin, respectively, and these myosin isoenzymes confer different ATPase activities, contractile velocities, and force. Skeletal muscle troponin has also diverged into fast and slow isoforms, but their functional significance is not fully understood. To investigate the expression of troponin isoforms in mammalian skeletal muscle and their functional relationship to that of the myosin isoforms, we concomitantly studied myosin, troponin T (TnT), and troponin I (TnI) isoform contents and isometric contractile properties in single fibers of rat skeletal muscle. We characterized a large number of Triton X-100-skinned single fibers from soleus, diaphragm, gastrocnemius, and extensor digitorum longus muscles and selected fibers with combinations of a single myosin isoform and a single class (slow or fast) of the TnT and TnI isoforms to investigate their role in determining contractility. Types IIa, IIx, and IIb myosin fibers produced higher isometric force than that of type I fibers. Despite the polyploidy of adult skeletal muscle fibers, the expression of fast or slow isoforms of TnT and TnI is tightly coupled. Fibers containing slow troponin had higher Ca2+ sensitivity than that of the fast troponin fibers, whereas fibers containing fast troponin showed a higher cooperativity of Ca2+ activation than that of the slow troponin fibers. These results demonstrate distinct but coordinated regulation of troponin and myosin isoform expression in skeletal muscle and their contribution to the contractile properties of muscle. [ABSTRACT FROM AUTHOR]

Purpose: Denervated skeletal muscles lack contractile activity and subsequently lose mass and force generation. Prolonged periods of denervation prior to nerve-implant grafting limit the recovery of mass and force. We hypothesized that electrical stimulation during a period of denervation that maintains mass and force above the levels of denervated muscles enhances the recovery of mass and force following nerve-implant grafting. Methods: The extensor digitorum longus (EDL) muscles of anesthetized rats were denervated, and a stimulator was implanted. Following 4 or 7 months of denervation, with or without electrical stimulation, the EDL muscles were removed, evaluated in vitro for mass and contractile properties, and then nerve-implant grafted into syngeneic rats. Unoperated, contralateral muscles were also evaluated and grafted. Results: The hypothesis was not supported by the experimental data. Compared with values for 4- or 7-month denervated muscles, the stimulated-denervated muscles maintained higher mass and force, less prolonged time-to-peak tensions and half-relaxation times, and higher excitability. Nevertheless, the recovery of mass and force following grafting was not improved. Conclusion: The factors within long-term denervated muscles that hinder recovery following grafting appear to be related primarily to factors associated with the duration of denervation and not to the level of atrophy and weakness prior to grafting. [ABSTRACT FROM AUTHOR]

We report here studies that integrate data of respiration rate from mouse skeletal muscle in response to leptin and pharmacological interference with intermediary metabolism, together with assays for phosphatidylinositol 3-kinase (PI3K) and AMP-activated protein kinase (AMPK). Our results suggest that the direct effect of leptin in stimulating thermogenesis in skeletal muscle is mediated by substrate cycling between de novo lipogenesis and lipid oxidation, and that this cycle requires both PI3K and AMPK signaling. This substrate cycling linking glucose and lipid metabolism to thermogenesis provides a novel thermogenic mechanism by which leptin protects skeletal muscle from excessive fat storage and lipotoxicity. [Copyright &y& Elsevier]

Glycogen supercompensation (increase in muscle glycogen content above basal) is an established phenomenon induced by unknown mechanisms. It consists of both insulin-dependent and -independent components. Here, we investigate insulin-independent glycogen supercompensation in isolated, intact extensor digitorum longus muscles from mice. Muscles were stimulated electrically, incubated in vitro with 5.5 mM glucose for up to 16 h and then analysed for glycogen, glucose uptake and enzyme activities. Basal glycogen was 84±6 µmol glucosyl units/g dry muscle and was depleted by 80% after 10 min contraction. Glycogen increased after contraction, reaching a peak value of 113±9 µmol glucosyl units/g dry muscle (P<0.05 vs. basal) by 6 h, and returned to basal values by 16 h (84±8). Maximal activities of glycogen synthase, phosphorylase and a-glucosidase were not significantly altered by contraction or during the 6-h recovery period. Glycogen synthase fractional activity (0.17/7.2 mM glucose-6-P; inversely related to phosphorylation state of the enzyme) was increased about twofold early after contraction but then decreased and was slightly lower than baseline during the period of supercompensation (4-6 h). Phosphorylase fractional activity (±adenosine monophosphate; directly related to phosphorylation state of the enzyme) decreased to 60% of basal after contraction and decreased further during the initial 4 h of recovery to 40% of basal (P<0.01 vs. basal). After 4 h recovery, glucose uptake was slightly (50%) higher in the stimulated than in the non-stimulated muscle (P<0.01). Thus, insulin-independent glycogen supercompensation involves inactivation of phosphorylase and hence an inhibition of glycogen breakdown. [ABSTRACT FROM AUTHOR]

Age-related changes in skeletal muscle, in combination with bed rest, may result in a poorer rehabilitation potential for an elderly patient. The purpose of this study was to determine the effects of non-weight bearing (hind limb unweighting [HU]) on the soleus and extensor digitorum longus (EDL) in older rats. Two non-weight bearing conditions were used: an uninterrupted bout of HU and an interrupted bout of HU. Twenty-one rats were randomly placed into 1 of 3 groups: control, interrupted HU (2 phases of 7 days of HU, separated by a 4-day weight-bearing phase) and an uninterrupted HU (18 uninterrupted days of HU). Following non-weight bearing, the soleus and EDL muscles were removed. Fiber type identification was performed by myofibrillar ATPase and cross-sectional area was determined. The findings suggest that any period of non-weight bearing leads to a decrease in muscle wet weight (19%-45%). Both type I and type H fibers of the soleus showed atrophy (decrease in cross-sectional area, 35%-44%) with an uninterrupted bout of non-weight bearing. Only the type II fibers of the soleus showed recovery with an interrupted bout of weight bearing. In the EDL, type II fibers were more affected by an uninterrupted bout of non-weight bear ing (15% decrease in fiber size) compared to the type I fibers. EDL type II fibers showed more atrophy with interrupted bouts of non-weight bearing than with a single bout (a 40% compared to a 15% decrease). This study shows that initial weight bearing after an episode of non-weight bearing may be damaging to type II fibers of the EDL. [ABSTRACT FROM AUTHOR]

We have investigated the expression and regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in fast extensor digitorum longus (EDL) and slow soleus (SOL) in adult rat skele-tal muscles. Biochemical assays revealed significantly greater PTK and PTP activities in SOL than in EDL; these results were confirmed and extended by in-gel assays demonstrating that the PTKs and PTPs detected had higher activity levels in SOL compared to EDL extracts. Although phosophotyrosine proteins were concentrated at the neuromuscular junction (NMJ), PTK and PTP activities were observed in extra-junctional regions of the muscle fiber. Following denervation, we observed significant increases in PTK and PTP activities in both SOL and EDL, and gel-based assays showed an increase in the activities of several PTKs and PTPs. These results suggest that the same PTK and PTPs have different activity levels in fast and slow skeletal muscles and are regulated by nerve-dependent mechanisms. [ABSTRACT FROM AUTHOR]

The present study highlights possible problems that can arise from the incorrect preparation of control and test solutions for use in Ca2+-activation experiments using single skinned skeletal muscle fibres and EGTA-based Ca2+ buffers. We show here, using glucose 6-phosphate (G6-P) as our "test" compound, that the Ca2+-activation properties of skinned single fibre segments from the extensor digitorum longus muscle of the rat are highly dependent on the form in which the G6-P is added and on the correct balancing of an appropriate anion in control solutions. Test solutions prepared by the direct addition of 10 mM monosodium G6-P salt to a set of control solutions of defined pCa resulted in significantly greater submaximal force responses than the corresponding controls. This is equivalent to an increase in the sensitivity of the contractile-regulatory system to Ca2+ (pCa50=–log10[Ca2+] that produces 50% of maximum force) by 0.19±0.01 pCa units. In contrast, addition of disodium G6-P to control solutions caused a slight reduction in the apparent sensitivity of the contractile apparatus to Ca2+ by 0.04±0.01 pCa units (P<0.01). Rather than being indicative of the effects of G6-P on the contractile apparatus, these opposing effects are due to differences between test and control solutions with respect to pH and Na+ concentration brought about by the G6-P salts. When all ionic species were carefully balanced, 10 mM G6-P was found to have only a small sensitizing effect on Ca2+-activation properties compared to control, without affecting the maximum Ca2+-activated force response. Our findings highlight the often-overlooked need for careful balancing of the ionic composition in control and test solutions when examining the true effects of different compounds on the Ca2+-activation characteristics of single skinned muscle fibre preparations. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Diabetes mellitus has a serious effect on most of the properties of skeletal muscles. Changes in neuromuscular transmission are also involved in propagating the disease. Methods. In our experiments, acetylcholinesterase was extracted from the fast extensor digitorum longus and slow soleus muscles of control, non-treated 6-week-diabetic and insulin-treated diabetic rats. The extracts were applied to velocity sedimentation and acetylcholinesterase activity was determined. Results. We observed considerable differences in the distribution of individual acetylcholinesterase molecular forms in diabetic fast muscles. This included a 59 % decline in G4 content together with a fivefold increase in A8 and a 53 % increase in A12 activity resulting in a shift of acetylcholinesterase profile characteristically towards slow muscles. These alterations were partly reversed by insulin treatment. Conclusion/interpretation. In slow muscles diabetes caused an increase in G4 activity without affecting the sedimentation profile. Decline in G4 content in fast muscles could contribute to enhanced desensitization of acetylcholine receptors in diabetes. [Diabetologia (2001) 44: 220–223] [ABSTRACT FROM AUTHOR]

In the present study we measured, for the first time, the isometric specific force (SF, force normalized to cross sectional area) generated by single intact fibers from fast- (extensor digitorum longus, EDL) and slow-twitch (soleus) muscles from young adult (2-6), middle-aged (12-14) and old (20-24 month-old) mice. SF has also been measured in single intact flexor digitorum brevis fibers from young mice. Muscle fibers have been classified into fast- or slow-twitch based on the contraction kinetics. Maximum SF recorded in EDL and soleus fibers from young and middle-aged mice did not differ significantly. A significant age-dependent decline in maximum SF was recorded in EDL and soleus fibers from young or middle-aged to old mice. The SF was 377 +/- 18, 417 +/- 20 and 279 +/- 18 kPa for EDL fibers from young, middle-aged and old mice, respectively and 397 +/- 17, 405 +/- 24 and 320 +/- 33 kPa for soleus fibers from age-matched mice, respectively. The frequency needed to elicit maximum force in EDL and soleus fibers from middle-aged to old mice did not differ significantly. In conclusion, the specific force developed by both fast and slow-twitch single intact muscle fibers declines with aging and more significantly in the former. [ABSTRACT FROM AUTHOR]