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Human Skeletal Muscle (human + skeletal_muscle)
Terms modified by Human Skeletal Muscle Selected AbstractsExercise Heat Stress does not Reduce Central Activation to non-exercised Human Skeletal MuscleEXPERIMENTAL PHYSIOLOGY, Issue 6 2003Julian Saboisky In this study we measured the central activation ratio (CAR) of the leg extensors and the elbow flexor muscles before and after exhaustive exercise in the heat to determine whether exercise-induced hyperthermia affects the CNS drive to exercised (leg extensors) and/or non-exercised (forearm flexors) muscle groups. Thirteen subjects exercised at fixed intensities representative of a percentage of peak power output (PPO) for 10 min periods (50%, 40%, 60%, 50%) and then at 75% PPO until exhaustion in ambient conditions of 39.3 ± 0.8 °C and 60.0 ± 0.8% relative humidity. Before and immediately following exercise subjects performed a series of maximal voluntary contractions (MVCs) with the leg extensors (exercised muscles) and forearm flexors (non-exercised muscles). The degree of voluntary activation during the sustained MVCs was assessed by superimposing electrical stimulation to the femoral nerve and the biceps brachii. Exercise to exhaustion increased the rectal temperature from 37.2 ± 0.2 to 38.8 ± 0.2 °C (P < 0.0001). The mean heart rate at the end of exercise to exhaustion was 192 ± 3 beats min,1. Leg extensor voluntary force was significantly reduced from 595 ± 143 to 509 ± 105 N following exercise-induced hyperthermia but forearm flexor force was similar before and after exercise. The CAR of the leg extensors decreased from 94.2 ± 1.3% before exercise to 91.7 ± 1.5% (P < 0.02) following exercise-induced hyperthermia. However, the CAR for the forearm flexors remained at similar levels before and after exercise. The data suggest that the central nervous system selectively reduces central activation to specific skeletal muscles as a consequence of exercise-induced hyperthermia. [source] Angiotensin-Converting Enzyme Genotype Affects the Response of Human Skeletal Muscle to Functional OverloadEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Jonathan Folland The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy , an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7%; ID, 17.6 ± 2.2%; DD, 14.9 ± 1.3%, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function. [source] Fibre Type Dependent Expression of Glucose Transporters in Human Skeletal MusclesAPMIS, Issue 2007Michael Gaster First page of article [source] Plasticity of human skeletal muscle: gene expression to in vivo functionEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Stephen D. R. Harridge Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (Vmax), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing Vmax and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level. [source] Resistance exercise increases leg muscle protein synthesis and mTOR signalling independent of sexACTA PHYSIOLOGICA, Issue 1 2010H. C. Dreyer Abstract Aim:, Sex differences are evident in human skeletal muscle as the cross-sectional area of individual muscle fibres is greater in men than in women. We have recently shown that resistance exercise stimulates mammalian target of rapamycin (mTOR) signalling and muscle protein synthesis in humans during early post-exercise recovery. Therefore, the aim of this study was to determine if sex influences the muscle protein synthesis response during recovery from resistance exercise. Methods:, Seventeen subjects, nine male and eight female, were studied in the fasted state before, during and for 2 h following a bout of high-intensity leg resistance exercise. Mixed muscle protein fractional synthetic rate was measured using stable isotope techniques and mTOR signalling was assessed by immunoblotting from repeated vastus lateralis muscle biopsy samples. Results:, Post-exercise muscle protein synthesis increased by 52% in the men and by 47% in the women (P < 0.05) and was not different between groups (P > 0.05). Akt phosphorylation increased in both groups at 1 h post-exercise (P < 0.05) and returned to baseline during 2 h post-exercise with no differences between groups (P > 0.05). Phosphorylation of mTOR and its downstream effector S6K1 increased significantly and similarly between groups during post-exercise recovery (P < 0.05). eEF2 phosphorylation decreased at 1- and 2 h post-exercise (P < 0.05) to a similar extent in both groups. Conclusion:, The contraction-induced increase in early post-exercise mTOR signalling and muscle protein synthesis is independent of sex and appears to not play a role in the sexual dimorphism of leg skeletal muscle in young men and women. [source] Training response of mitochondrial transcription factors in human skeletal muscleACTA PHYSIOLOGICA, Issue 1 2010J. Norrbom Abstract Aim:, Mitochondrial function is essential for physical performance and health. Aerobic fitness is positively associated with mitochondrial (mt) biogenesis in muscle cells through partly unknown regulatory mechanisms. The present study aimed to investigate the influence of exercise and training status on key mt transcription factors in relation to oxidative capacity in human skeletal muscle. Methods:, The basal mRNA and protein levels of mitochondrial transcription factor A (TFAM), mitochondrial transcription factors B1 (TFB1M) or B2 (TFB2M), and mRNA levels of mitochondrial transcription termination factor (mTERF), were measured in a cross-sectional study with elite athletes (EA) and moderately active (MA) and the basal mRNA levels of these factors were measured during a 10-day endurance training programme with (R-leg) and without (NR-leg) restricted blood flow to the working leg. Results:, TFAM protein expression was significantly higher in the EA than in the MA, while protein levels of TFB1M and TFB2M were not different between the groups. There was no difference between EA and MA, or any effect with training on TFAM mRNA levels. However, the mRNA levels of TFB1M, TFB2M and mTERF were higher in EA compared with MA. For TFB1M and TFB2M, the mRNA expression was increased in the R-leg after 10 days of training, but not in the NR-leg. mTERF mRNA levels were higher in EA compared with MA. Conclusion:, This study further establishes that TFAM protein levels are higher in conditions with enhanced oxidative capacity. The mRNA levels of TFB1M and TFB2M are influenced by endurance training, possibly suggesting a role for these factors in the regulation of exercise-induced mitochondrial biogenesis. [source] Oestradiol and SERM treatments influence oestrogen receptor coregulator gene expression in human skeletal muscle cellsACTA PHYSIOLOGICA, Issue 3 2009C. M. Dieli-Conwright Abstract Aim:, Oestrogen receptors (ER) are present in human skeletal muscle (hSkM) cells; however, the function of the receptor is currently unknown. We investigated the influence of oestradiol and selective ER modulators [tamoxifen (TAM), raloxifene (RAL)] on ER coregulator mRNA expression in hSkM. Methods:, Human skeletal muscle cells were treated with 10 nm oestradiol, 5 ,m TAM and 10 ,m RAL over a 24-h period. Following the treatment period, mRNA expression was quantified using real-time PCR to detect changes in ER-,, ER-,, steroid receptor coactivator (SRC), silencing mediator for retinoid and thyroid hormone receptors (SMRT), MyoD, GLUT4 and c-fos. Results:, ER-, mRNA expression increased with all three drug treatments (P < 0.05) while there was no change in mRNA expression of ER-, in hSkM cells. mRNA expression of SRC increased and SMRT decreased with oestradiol, TAM and RAL in hSkM cells (P < 0.05). Importantly, mRNA expression of MyoD increased with oestradiol and decreased with TAM and RAL in hSkM cells (P < 0.05). mRNA expression of GLUT4 increased with oestradiol and RAL and decreased with TAM in hSkM cells (P < 0.05). Conclusions:, These findings are novel in that they provide the first evidence that oestradiol and selective ER modulators influence ER-, function in hSkM cells. This demonstrates the importance of the ER and alterations in its coregulators, to potentially prevent sarcopenia and promote muscle growth in postmenopausal women using these forms of hormone replacement therapy. [source] Expression of Na+/HCO3, co-transporter proteins (NBCs) in rat and human skeletal muscleACTA PHYSIOLOGICA, Issue 1 2004J. M. Kristensen Abstract Aim:, Sodium/bicarbonate co-transport (NBC) has been suggested to have a role in muscle pH regulation. We investigated the presence of NBC proteins in rat and human muscle samples and the fibre type distribution of the identified NBCs. Methods and results:, Western blotting of muscle homogenates and sarcolemmal membranes (sarcolemmal giant vesicles) were used to screen for the presence of NBCs. Immunohistochemistry was used for the subcellular localization. The functional test revealed that approximately half of the pH recovery in sarcolemmal vesicles produced from rat muscle is mediated by bicarbonate-dependent transport. This indicates that the NBCs are preserved in the vesicles. The western blotting experiments demonstrated the existence of at least two NBC proteins in skeletal muscle. One NBC protein (approximately 150 kDa) seems to be related to the kidney/pancreas/heart isoform NBC1, whereas the other protein (approximately 200 kDa) is related to the NBC4 isoform. The two NBC proteins represent the electrogenic isoforms named NBCe1 and NBCe2. Membrane fractionation and immunofluorescence techniques confirmed that the two NBCs are located in the sarcolemmal membrane as well as in some internal membranes, probably the T-tubules. The two NBCs localized in muscle have distinct fibre type distributions. Conclusions:, Skeletal muscle possesses two variants of the sodium/bicarbonate co-transporter (NBC) isoforms, which have been called NBCe1 and NBCe2. [source] Oestrogen receptor , is expressed in adult human skeletal muscle both at the mRNA and protein levelACTA PHYSIOLOGICA, Issue 4 2003A. Wiik Abstract Aim:, There are two known oestrogen receptors (ER), oestrogen receptor , (ER,) and the recently cloned oestrogen receptor , (ER,). ER, mRNA has been detected in mouse, rat, bovine and human skeletal muscle. ER, mRNA has been detected in bovine skeletal muscle. To our knowledge, no study has investigated the expression of oestrogen receptor , in human skeletal muscle. Therefore, the primary aim of the present investigation was to study ER, mRNA and protein expression in human skeletal muscle. In addition the ER, expression was also studied. Methods:, Muscle biopsies were taken from vastus lateralis in six healthy adults (three women and three men). mRNA expression was detected with real-time PCR (TaqMan) and protein localization by immunohistochemistry. Results:, A clear expression of ER, and ER, mRNA was seen in skeletal muscle in all subjects. The ER, mRNA expression was 180 fold higher compared with that of ER, mRNA. Immunohistochemistry demonstrated positive staining for ER,, but not for ER,, with localization to the nuclei of skeletal muscle fibres. On average, 70% of all nuclei were ER, -positive. Conclusion:, The present study shows for the first time ER, mRNA and protein expression in human skeletal muscle tissue in both males and females. [source] Muscle fibre size and capillarity in Korean diving womenACTA PHYSIOLOGICA, Issue 2 2003K. A. Bae Abstract Aim:, Effects of prolonged habitual cold-water immersion on fibre size and capillarity in vastus lateralis muscle were studied in human beings. The hypothesis tested in the present study was that cold acclimatized human skeletal muscle would have reduced muscle fibre size and higher capillarity, favouring the idea of efficacy of recruitment under cold environment. Methods:, Ten women breath-hold divers (BHDs) and 10 active women (controls CONs) participated in this study. Muscle biopsy was obtained from vastus lateralis and determined fibre type composition and capillary density. Results: A major finding was that all BHDs revealed a markedly smaller cross-sectional area (CSA) in all fibre types than the CONs, or even than any other morphological data reported in previous investigations. Furthermore, mean CSA of type II fibre (range 1205,2766 ,m2) was much smaller than type I fibre (2343,4327 ,m2). The number of capillaries per fibre in different fibre types in the BHDs was higher than in the CONs (P < 0.001), and diffusional area was smaller in type II fibres than in type I fibres (P < 0.001). The BHDs and the CONs have similarity in the percentage of type I fibres, but type II fibre was predominant in both groups. Interestingly the proportion of type IIx fibre in the BHDs was higher (31%) than in the CONs (22%). No significant difference was found in the thigh circumference between the groups. Conclusion:, The present study demonstrates that prolonged habitual cold-water immersion may induce a decrease in fibre size and an increase in capillarity in human skeletal muscle. [source] Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistanceEXPERIMENTAL PHYSIOLOGY, Issue 1 2010T. Fuentes To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin signalling and signal transducer and activator of transcription 3 (STAT3) phosphorylation and reduce AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) phosphorylation. Deltoid and vastus lateralis muscle biopsies were obtained from 20 men: 10 non-obese control subjects (mean ±s.d. age, 31 ± 5 years; height, 184 ± 9 cm; weight, 91 ± 13 kg; and percentage body fat, 24.8 ± 5.8%) and 10 obese (age, 30 ± 7 years; height, 184 ± 8 cm; weight, 115 ± 8 kg; and percentage body fat, 34.9 ± 5.1%). Skeletal muscle OB-R170 (OB-R long isoform) protein expression was 28 and 25% lower (both P < 0.05) in arm and leg muscles, respectively, of obese men compared with control subjects. In normal-weight subjects, SOCS3 protein expression, and STAT3, AMPK, and ACC, phosphorylation, were similar in the deltoid and vastus lateralis muscles. In obese subjects, the deltoid muscle had a greater amount of leptin receptors than the vastus lateralis, whilst SOCS3 protein expression was increased and basal STAT3, AMPK, and ACC, phosphorylation levels were reduced in the vastus lateralis compared with the deltoid muscle (all P < 0.05). In summary, skeletal muscle leptin receptors and leptin signalling are reduced in obesity, particularly in the leg muscles. [source] Plasticity of human skeletal muscle: gene expression to in vivo functionEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Stephen D. R. Harridge Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (Vmax), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing Vmax and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level. [source] Body maintenance and repair: how food and exercise keep the musculoskeletal system in good shapeEXPERIMENTAL PHYSIOLOGY, Issue 4 2005Michael J. Rennie This article provides a personal view of how feeding and exercise acutely modify protein metabolism of human skeletal muscle, with discussion of the anabolic signalling mechanisms involved and some new findings on the metabolism of the turnover of collagen, tendon and bone. [source] Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1)JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2001Enders Kai On Ng Abstract We have cloned and characterized another alternatively spliced isoform of the human four-and-a-half LIM domain protein 1 (FHL1), designated FHL1C. FHL1C contains a single zinc finger and two tandem repeats of LIM domains at the N-terminus followed by a putative RBP-J binding region at the C-terminus. FHL1C shares the same N-terminal two-and-a-half LIM domains with FHL1 but different C-terminal protein sequences. Due to the absence of the exon 4 in FHL1C, there is a frame-shift in the 3, coding region. Sequence analysis indicated that FHL1C is the human homolog of murine KyoT2. The Northern blot and RT-PCR results revealed that FHL1 is widely expressed in human tissues, including skeletal muscle and heart at a high level, albeit as a relatively low abundance transcript in brain, placenta, lung, liver, kidney, pancreas, and testis. In contrast, FHL1C is specifically expressed in testis, skeletal muscle, and heart at a relatively low level compared with FHL1. The expression of FHL1C transcripts was also seen in aorta, left atrium, left, and right ventricles of human heart at low level. Immunoblot analysis using affinity-purified anti-FHL1C antipeptide antibodies confirmed a 20 kDa protein of FHL1C in human skeletal muscle and heart. Unlike FHL1B, which is another FHL1 isoform recently reported by our group and localized predominantly in the nucleus [Lee et al., 1999], FHL1C is localized both in the nucleus and cytoplasm of mammalian cell. J. Cell. Biochem. 82: 1,10, 2001. © 2001 Wiley-Liss, Inc. [source] Bile acids and insulin resistance: implications for treating nonalcoholic fatty liver diseaseJOURNAL OF DIGESTIVE DISEASES, Issue 2 2009Jue WEI Nonalcoholic fatty liver disease is characterized by an accumulation of excess triglycerides in hepatocytes, and insulin resistance is now considered the fundamental operative mechanism throughout the prevalence and progression of the disease. Besides their role in dietary lipid absorption and cholesterol homeostasis, evidence has accumulated that bile acids are also signaling molecules that play two important roles in glucose and lipid metabolism: in the nuclear hormone receptors as farnesoid X receptors (FXR), as well as ligands for G-protein-coupled receptors TGR5. The activated FXR-SHP pathway regulates the enterohepatic recycling and biosynthesis of bile acids and underlies the down-regulation of hepatic fatty acid and triglyceride biosynthesis and very low density lipoprotein production mediated by sterol-regulatory element-binding protein-1c. The bile acid-TGR5-cAMP-D2 signaling pathway in human skeletal muscle in the fasting,feeding cycle increases energy expenditure and prevents obesity. Therefore, a molecular basis has been provided for a link between bile acids, lipid metabolism and glucose homeostasis, which can open novel pharmacological approaches against insulin resistance and nonalcoholic fatty liver disease. [source] Regenerative potential of human skeletal muscle during agingAGING CELL, Issue 2 2002Valérie Renault Summary In this study, we have investigated the consequences of aging on the regenerative capacity of human skeletal muscle by evaluating two parameters: (i) variation in telomere length which was used to evaluate the in vivo turn-over and (ii) the proportion of satellite cells calculated as compared to the total number of nuclei in a muscle fibre. Two skeletal muscles which have different types of innervation were analysed: the biceps brachii, a limb muscle, and the masseter, a masticatory muscle. The biopsies were obtained from two groups: young adults (23 ± 1.15 years old) and aged adults (74 ± 4.25 years old). Our results showed that during adult life, minimum telomere lengths and mean telomere lengths remained stable in the two muscles. The mean number of myonuclei per fibre was lower in the biceps brachii than in the masseter but no significant change was observed in either muscle with increasing age. However, the number of satellite cells, expressed as a proportion of myonuclei, decreased with age in both muscles. Therefore, normal aging of skeletal muscle in vivo is reflected by the number of satellite cells available for regeneration, but not by the mean number of myonuclei per fibre or by telomere lengths. We conclude that a decrease in regenerative capacity with age may be partially explained by a reduced availability of satellite cells. [source] Resolution of creatine and phosphocreatine 1H signals in isolated human skeletal muscle using HR-MAS 1H NMRMAGNETIC RESONANCE IN MEDICINE, Issue 6 2008Jin-Hong Chen Abstract Proton NMR spectra of freshly isolated human skeletal muscle samples contain creatine and phosphocreatine resonances with distinct chemical shifts that are easily visualized with magic angle spinning (MAS, spinning the sample rapidly at 54.7° with respect to the magnetic field) methods. The identification of the phosphocreatine resonance was based on two findings: that (i) the possible small dipolar coupling does not contribute to line splitting under rapid MAS, and (ii) the 1H signal decreases concurrently with the phosphocreatine resonance observed in 31P NMR experiments. In the MAS 1H spectra, the phosphocreatine resonance remains a singlet with a linewidth of less than 3 Hz. The creatine resonances are split into two peaks with linewidths at half height of approximately 2 and 6 Hz, respectively. The resonance with the broader linewidth represents creatine that is significantly motion-restricted and suggests that a creatine pool in muscle tissue is highly compartmentalized. Magn Reson Med 59:1221,1224, 2008. © 2008 Wiley-Liss, Inc. [source] Muscle biopsy substantiates long-term MRI alterations one year after a single dose of botulinum toxin injected into the lateral gastrocnemius muscle of healthy volunteers,MOVEMENT DISORDERS, Issue 10 2009A. Sebastian Schroeder MD Abstract Despite numerous clinical and experimental studies on botulinum toxin type A (BoNT/A), long-term alterations of muscle texture and fine structure following BoNT/A treatment have thus far not been studied in normal human skeletal muscle. After obtaining institutional review board approval, we performed a prospective, placebo-controlled, double-blinded follow-up study on two healthy adults using magnetic resonance imaging (MRI) and muscle biopsy to visualize long-term alterations after a single BoNT/A injection into the lateral head of the gastrocnemius muscle. MRI disclosed a high-signal-intensity pattern in short tau inversion recovery sequences, and a reduction of the cross-sectional area in the BoNT/A-injected, but not in the saline-injected contralateral control muscle (at 6 to 9 months in volunteer A: 73%, in B: 62%; at 12 months in A: 88%, and in B: 78%). Enzyme histochemistry, 12 months after injection, confirmed neurogenic atrophy of muscle fibers only in the BoNT/A-injected muscle. Electron microscopy revealed additional degenerative changes at the neuromuscular junction. The data confirm that MRI is a suitable tool to monitor the long-term effect of BoNT/A on skeletal muscle. Neurogenic muscle atrophy following a single BoNT/A injection should be taken into consideration when repeated BoNT/A injections into the same muscles are proposed. © 2009 Movement Disorder Society [source] Impact of varying pulse frequency and duration on muscle torque production and fatigue,MUSCLE AND NERVE, Issue 4 2007Chris M. Gregory PhD Abstract Neuromuscular electrical stimulation (NMES) involves the use of electrical current to facilitate contraction of skeletal muscle. However, little is known concerning the effects of varying stimulation parameters on muscle function in humans. The purpose of this study was to determine the extent to which varying pulse duration and frequency altered torque production and fatigability of human skeletal muscle in vivo. Ten subjects underwent NMES-elicited contractions of varying pulse frequencies and durations as well as fatigue tests using stimulation trains of equal total charge, yet differing parametric settings at a constant voltage. Total charge was a strong predictor of torque production, and pulse trains with equal total charge elicited identical torque output. Despite similar torque output, higher- frequency trains caused greater fatigue. These data demonstrate the ability to predictably control torque output by simultaneously controlling pulse frequency and duration and suggest the need to minimize stimulation frequency to control fatigue. Muscle Nerve, 2007 [source] Measuring the acute effect of insulin infusion on ATP turnover rate in human skeletal muscle using phosphorus-31 magnetic resonance saturation transfer spectroscopyNMR IN BIOMEDICINE, Issue 8 2010Ee Lin Lim Abstract Mitochondrial dysfunction has been proposed to underlie the insulin resistance of type 2 diabetes. However, the relative time course of insulin action in stimulating ATP turnover rate and glucose uptake in skeletal muscle has not been examined. These two parameters were measured in young healthy subjects using the 31P MRS saturation transfer method in conjunction with the euglycaemic hyperinsulinaemic clamp technique respectively. Glucose infusion rate rose rapidly from 0 to 2.90,±,0.11,mg/kgffm/min during the first 10,min of insulin infusion and further to 6.17,±,0.57,mg/kgffm/min between 15 and 45,min. In contrast, baseline ATP turnover rate was 9.0,±,0.4,µmol/g/min of muscle and did not change during the first 45,min of insulin infusion. Between 50 and 80,minutes ATP turnover rate increased by 8% and remained steady to 150,minutes (9.7,±,0.5 µmol/g/min of muscle, p,=,0.03 vs baseline). The in vivo time course of insulin stimulation of skeletal muscle ATP turnover rate is not consistent with a rate limiting effect upon the initiation of insulin-stimulated glycogen synthesis. Copyright © 2010 John Wiley & Sons, Ltd. [source] In vivo31P MRS detection of an alkaline inorganic phosphate pool with short T1 in human resting skeletal muscleNMR IN BIOMEDICINE, Issue 8 2010H. E. Kan Abstract Non-invasive determination of mitochondrial content is an important objective in clinical and sports medicine. 31P MRS approaches to obtain information on this parameter at low field strength typically require in-magnet exercise. Direct observation of the intra-mitochondrial inorganic phosphate (Pi) pool in resting muscle would constitute an alternative, simpler method. In this study, we exploited the higher spectral resolution and signal-to-noise at 7T to investigate the MR visibility of this metabolite pool. 31P in vivo MR spectra of the resting soleus (SOL) muscle were obtained with 1H MR image-guided surface coil localization (six volunteers) and of the SOL and tibialis anterior (TA) muscle using 2D CSI (five volunteers). A resonance at a frequency 0.38,ppm downfield from the cytosolic Pi resonance (Pi1; pH 7.0,±,0.04) was reproducibly detected in the SOL muscle in all subjects and conditionally attributed to the intra-mitochondrial Pi pool (Pi2; pH 7.3,±,0.07). In the SOL muscle, the Pi2/Pi1 ratio was 1.6 times higher compared to the TA muscle in the same individual. Localized 3D CSI results showed that the Pi2 peak was present in voxels well away from blood vessels. Determination of the T1 of the two Pi pools in a single individual using adiabatic excitation of the spectral region around 5,ppm yielded estimates of 4.3,±,0.4 s vs 1.4,±,0.5 s for Pi1 and Pi2, respectively. Together, these results suggest that the intra-mitochondrial Pi pool in resting human skeletal muscle may be visible with 31P MRS at high field. Copyright © 2010 John Wiley & Sons, Ltd. [source] Quantitative ATP synthesis in human liver measured by localized 31P spectroscopy using the magnetization transfer experimentNMR IN BIOMEDICINE, Issue 5 2008A. I. Schmid Abstract The liver plays a central role in intermediate metabolism. Accumulation of liver fat (steatosis) predisposes to various liver diseases. Steatosis and abnormal muscle energy metabolism are found in insulin-resistant and type-2 diabetic states. To examine hepatic energy metabolism, we measured hepatocellular lipid content, using proton MRS, and rates of hepatic ATP synthesis in vivo, using the 31P magnetization transfer experiment. A suitable localization scheme was developed and applied to the measurements of longitudinal relaxation times (T1) in six healthy volunteers and the ATP-synthesis experiment in nine healthy volunteers. Liver 31P spectra were modelled and quantified successfully using a time domain fit and the AMARES (advanced method for accurate, robust and efficient spectral fitting of MRS data with use of prior knowledge) algorithm describing the essential components of the dataset. The measured T1 relaxation times are comparable to values reported previously at lower field strengths. All nine subjects in whom saturation transfer was measured had low hepatocellular lipid content (1.5,±,0.2% MR signal; mean,±,SEM). The exchange rate constant (k) obtained was 0.30,±,0.02,s,1, and the rate of ATP synthesis was 29.5,±,1.8,mM/min. The measured rate of ATP synthesis is about three times higher than in human skeletal muscle and human visual cortex, but only about half of that measured in perfused rat liver. In conclusion, 31P MRS at 3,T provides sufficient sensitivity to detect magnetization transfer effects and can therefore be used to assess ATP synthesis in human liver. Copyright © 2007 John Wiley & Sons, Ltd. [source] An Analysis of the Microsporidian Genus Brachiola, with Comparisons of Human and Insect Isolates of Brachiola algeraeTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 6 2004ANN CALI ABSTRACT The genus Brachiola is the newest microsporidian genus established for a human infection with the type species being B. vesicularum in skeletal muscle. Subsequently, the microsporidium, Nosema algerae, identified from mosquitoes, was added to this genus because of morphological and physiological similarities. The present report illustrates a confirmed case of Brachiola algerae infecting skeletal muscle in a 56-year-old woman who was being treated for rheumatoid arthritis with immunosuppressive drugs. In the following study, these two human-infecting microsporidian species are ultrastructurally compared from human biopsy tissue. Additionally, Brachiola algerae from mosquitoes as reference B. algerae, was grown in athymic mice and compared to the human isolate in vivo, and in culture. B. algerae is morphologically identical in the host situations presented and different from B. vesicularum in human skeletal muscle. B. algerae has a consistently, slightly longer spore that typically contains one row of polar filament coils, while B. vesicularum typically contains two rows of polar filament coils and occasionally, one or three rows. In proliferative development, B. vesicularum forms protoplasmic extensions which do not occur on B. algerae, nor have they been reported on any other microsporidium. This report demonstrates that B. vesicularum and B. algerae are two different species of Brachiola that infect human skeletal muscle. [source] Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor , coactivator-1, mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscleTHE JOURNAL OF PHYSIOLOGY, Issue 10 2010Brendan Egan Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator-activated receptor , coactivator-1, (PGC-1,)-dependent transcriptional programmes. The purpose of this study was to determine if the intensity of exercise regulates PGC-1, expression in human skeletal muscle, coincident with activation of signalling cascades known to regulate PGC-1, transcription. Eight sedentary males expended 400 kcal (1674 kj) during a single bout of cycle ergometer exercise on two separate occasions at either 40% (LO) or 80% (HI) of,. Skeletal muscle biopsies from the m. vastus lateralis were taken at rest and at +0, +3 and +19 h after exercise. Energy expenditure during exercise was similar between trials, but the high intensity bout was shorter in duration (LO, 69.9 ± 4.0 min; HI, 36.0 ± 2.2 min, P < 0.05) and had a higher rate of glycogen utilization (P < 0.05). PGC-1, mRNA abundance increased in an intensity-dependent manner +3 h after exercise (LO, 3.8-fold; HI, 10.2-fold, P < 0.05). AMP-activated protein kinase (AMPK) (2.8-fold, P < 0.05) and calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation (84%, P < 0.05) increased immediately after HI but not LO. p38 mitogen-activated protein kinase (MAPK) phosphorylation increased after both trials (,2.0-fold, P < 0.05), but phosphorylation of the downstream transcription factor, activating transcription factor-2 (ATF-2), increased only after HI (2.4-fold, P < 0.05). Cyclic-AMP response element binding protein (CREB) phosphorylation was elevated at +3 h after both trials (,80%, P < 0.05) and class IIa histone deacetylase (HDAC) phosphorylation increased only after HI (2.0-fold, P < 0.05). In conclusion, exercise intensity regulates PGC-1, mRNA abundance in human skeletal muscle in response to a single bout of exercise. This effect is mediated by differential activation of multiple signalling pathways, with ATF-2 and HDAC phosphorylation proposed as key intensity-dependent mediators. [source] Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophyTHE JOURNAL OF PHYSIOLOGY, Issue 8 2009Séverine Lamon Skeletal muscle atrophy is a severe consequence of ageing, neurological disorders and chronic disease. Identifying the intracellular signalling pathways controlling changes in skeletal muscle size and function is vital for the future development of potential therapeutic interventions. Striated activator of Rho signalling (STARS), an actin-binding protein, has been implicated in rodent cardiac hypertrophy; however its role in human skeletal muscle has not been determined. This study aimed to establish if STARS, as well as its downstream signalling targets, RhoA, myocardin-related transcription factors A and B (MRTF-A/B) and serum response factor (SRF), were increased and decreased respectively, in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. The mRNA levels of the SRF target genes involved in muscle structure, function and growth, such as ,-actin, myosin heavy chain IIa (MHCIIa) and insulin-like growth factor-1 (IGF-1), were also measured. Following resistance training, STARS, MRTF-A, MRTF-B, SRF, ,-actin, MHCIIa and IGF-1 mRNA, as well as RhoA and nuclear SRF protein levels were all significantly increased by between 1.25- and 3.6-fold. Following the de-training period all measured targets, except for RhoA, which remained elevated, returned to base-line. Our results show that the STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy. [source] Exercise induces expression of leukaemia inhibitory factor in human skeletal muscleTHE JOURNAL OF PHYSIOLOGY, Issue 8 2008Christa Broholm The leukaemia inhibitory factor (LIF) belongs to the interleukin (IL)-6 cytokine superfamily and is constitutively expressed in skeletal muscle. We tested the hypothesis that LIF expression in human skeletal muscle is regulated by exercise. Fifteen healthy young male volunteers performed either 3 h of cycle ergometer exercise at ,60% of (n= 8) or rested (n= 7). Muscle biopsies were obtained from the vastus lateralis prior to exercise, immediately after exercise, and at 1.5, 3, 6 and 24 h post exercise. Control subjects had biopsy samples taken at the same time points as during the exercise trial. Skeletal muscle LIF mRNA increased immediately after the exercise and declined gradually during recovery. However, LIF protein was unchanged at the investigated time points. Moreover, we tested the hypothesis that LIF mRNA and protein expressions are modulated by calcium (Ca2+) in primary human skeletal myocytes. Treatment of myocytes with the Ca2+ ionophore, ionomycin, for 6 h resulted in an increase in both LIF mRNA and LIF protein levels. This finding suggests that Ca2+ may be involved in the regulation of LIF in endurance-exercised skeletal muscle. In conclusion, primary human skeletal myocytes have the capability to produce LIF in response to ionomycin stimulation and LIF mRNA levels increase in skeletal muscle following concentric exercise. The finding that the increase in LIF mRNA levels is not followed by a similar increase in skeletal muscle LIF protein suggests that other exercise stimuli or repetitive stimuli are necessary in order to induce a detectable accumulation of LIF protein. [source] The time course of the motoneurone afterhyperpolarization is related to motor unit twitch speed in human skeletal muscleTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003E. Roderich Gossen The relationship between the electrophysiological properties of motoneurones and their muscle units has been established in animal models. A functionally significant relationship exists whereby motoneurones with long post-spike afterhyperpolarizations (AHPs) innervate slow contracting muscle units. The purpose of this study was to determine whether the time course of the AHP as measured by its time constant is associated with the contractile properties of its muscle unit in humans. Using an intramuscular fine wire electrode, 46 motor units were recorded in eight subjects as they held a low force contraction of the first dorsal interosseus muscle for approximately 10 min. By applying a recently validated transform to the interspike interval histogram, the mean voltage versus time trajectory of the motoneurone AHP was determined. Spike-triggered averaging was used to extract the muscle unit twitch from the whole muscle force with strict control over force variability and motor unit discharge rate (interspike intervals between 120 and 200 ms). The AHP time constant was positively correlated to the time to half-force decay (,= 0.36, P < 0.05) and twitch duration (,= 0.57, P < 0.001); however, time to peak force failed to reach significance (,= 0.27, P < 0.07). These results suggest that a similar functional relationship exists in humans between the motoneurone AHP and the muscle unit contractile properties. [source] Cystic fibrosis transmembrane conductance regulator in human muscle: Dysfunction causes abnormal metabolic recovery in exerciseANNALS OF NEUROLOGY, Issue 6 2010Anne-Marie Lamhonwah PhD Objective Individuals with cystic fibrosis (CF) have exercise intolerance and skeletal muscle weakness not solely attributable to physical inactivity or pulmonary function abnormalities. CF transmembrane conductance regulator (CFTR) has been demonstrated in human bronchial smooth and cardiac muscle. Using 31P-magnetic resonance spectroscopy of skeletal muscle, we showed CF patients to have lower resting muscle adenosine triphosphate and delayed phosphocreatine recovery times after high-intensity exercise, suggesting abnormal muscle aerobic metabolism; and higher end-exercise pH values, suggesting altered bicarbonate transport. Our objective was to study CFTR expression in human skeletal muscle. Methods and Results We studied CFTR expression in human skeletal muscle by Western blot with anti-CFTR antibody (Ab) L12B4 and demonstrated a single band with expected molecular weight of 168kDa. We isolated the cDNA by reverse transcription polymerase chain reaction and directly sequenced a 975bp segment (c. 3,600,4,575) that was identical to the human CFTR sequence. We showed punctate staining of CFTR in sarcoplasm and sarcolemma by immunofluorescence microscopy with L12B4 Ab and secondary Alexa 488-labeled Ab. We confirmed CFTR expression in the sarcotubular network and sarcolemma by electron microscopy, using immunogold-labeled anti-CFTR Ab. We observed activation of CFTR Cl, channels with iodide efflux, on addition of forskolin, 3-isobutyl-1-methyl-xanthine, and 8-chlorphenylthio,cyclic adenosine monophosphate, in wild-type C57BL/6J isolated muscle fibers in contrast to no efflux from mutant F508del-CFTR muscle. Interpretation We speculate that a defect in sarcoplasmic reticulum CFTR Cl, channels could alter the electrochemical gradient, causing dysregulation of Ca2+ homeostasis, for example, ryanodine receptor or sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatases essential to excitation-contraction coupling leading to exercise intolerance and muscle weakness in CF. ANN NEUROL 2010 [source] Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophyANNALS OF NEUROLOGY, Issue 1 2010Mohammad Salajegheh MD Objective We investigated interferon-stimulated gene 15 (ISG15), a poorly understood ubiquitin-like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle and skin. Methods We generated microarray data measuring transcript abundance for approximately 18,000 genes in each of 113 human muscle biopsy specimens, and studied biopsy specimens and cultured skeletal muscle using immunohistochemistry, immunoblotting proteomics, real-time quantitative polymerase chain reaction, and laser-capture microdissection. Results Transcripts encoding ISG15-conjugation pathway proteins were markedly upregulated in DM with perifascicular atrophy (DM-PFA) muscle (ISG15 339-fold, HERC5 62-fold, and USP18 68-fold) compared with 99 non-DM samples. Combined analysis with publicly available microarray datasets showed that >50-fold ISG15 transcript elevation had 100% sensitivity and specificity for 28 biopsies from adult DM-PFA and juvenile DM patients compared with 199 muscle samples from other muscle diseases. Free ISG15 and ISG15-conjugated proteins were only found on immunoblots from DM-PFA muscle. Cultured human skeletal muscle exposed to type 1 interferons produced similar transcripts and ISG15 protein and conjugates. Laser-capture microdissection followed by proteomic analysis showed deficiency of titin in DM perifascicular atrophic myofibers. Interpretation A large-scale microarray study of muscle samples demonstrated that among a diverse group of muscle diseases DM was uniquely associated with upregulation of the ISG15 conjugation pathway. Exposure of human skeletal muscle cell culture to type 1 interferons produced a molecular picture highly similar to that seen in human DM muscle. Perifascicular atrophic myofibers in DM were deficient in a number of skeletal muscle proteins including titin. ANN NEUROL 2010;67:53,63 [source] Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysisANNALS OF NEUROLOGY, Issue 3 2001Saďd Bendahhou PhD A novel mutation in a family with hypokalemic periodic paralysis is described. The mutation R672S is located in the voltage sensor segment S4 of domain II in the SCN4A gene encoding the human skeletal muscle voltage-gated sodium channel. Functional expression of the R672S channels in human embryonic kidney 293 cells revealed a small but significant hyperpolarizing shift in the steady-state fast inactivation, and a dramatic enhancement in channel slow inactivation. These two defects are mainly due to a slow recovery of the mutant channels from fast and/or slow inactivation. Our data may help explain the mechanism underlying hypokalemic periodic paralysis and the patient's worsening from acetazolamide. [source] |