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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Senile muscle atrophy is a characteristic feature of advancing age. Despite the growing body of knowledge about weight-bearing muscles in rodents and man, there is relatively little such information on the muscles of mastication. Therefore, the primary goal here was to develop a masseter muscle preparation from male Fischer 344 rats suitable for studying contractile characteristics in vitro. And, secondarily, the goal was to examine this preparation for evidence of age-related changes in muscle composition and function in rats aged 4--24 months. Histochemical analysis of the composition of the four anatomical regions (branches) of the masseter revealed a mixture of rapidly contracting, fatiguable and fatigue-resistant muscle fibres with no significant differences between branches. Fibre type and size were determined with myosin ATPase, NADH-TR and toluidine blue staining of quick- frozen muscle sections. No significant changes in fibre type or fibre area were found with increasing age. One branch of the masseter, the anterior deep masseter, is sufficiently thin (less than 0.8 mm thickness) for adequate diffusion of oxygen and nutrients in studies of isometric contractile properties in vitro. Contraction time, half-relaxation time, dry weight:wet weight ratio and maximum force per unit area were found to be similar in muscles of young and old rats. Our results demonstrate that the anterior deep masseter of the rat is a suitable preparation for investigating masseter function in vitro. The surprising absence of age-related changes in composition and function is consistent with some, but not all, data on ageing rodent limb muscles. The results suggest that masticatory muscle performance is preserved with age in rats.
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PMID:Constancy of masseter muscle structure and function with age in F344 rats. 1116 21

The aim of this study was to evaluate myofibrillar creatine kinase (CK) activity and to quantify the substrate channelling of ATP between CK and myosin ATPase under different pH conditions within the integrity of myofibrils. A pure myofibrillar fraction was prepared using differential centrifugation. The homogeneity of the preparation and the purity of the fraction were confirmed microscopically and by enzymatic assays for contaminant enzyme activities. The specific activity of myofibrillar CK reached 584 +/- 33 nmol PCr min(-1) mg(-1) at pH 6.75. Two methods were used to detect CK activity: (1) measurement of direct ATP production, and (2) measurement of PCr consumption. This method of evaluation has been tested in experiments with isolated creatine kinase. No discrepancy in CK activity between the methods was observed in the pH range tested (6.0-7.5). However, the same procedures resulted in a significant discrepancy between the amounts of reacted PCr and produced ATP within the pure myofibrillar fraction. This discrepancy represents the portion of ATP produced by the CK reaction, which is preferentially channelled to the myosin ATPase before diffusing into the bulk solution. The maximum evaluated difference reached 42.3 % at pH 6.95. The substrate channelling between myofibrillar-bound CK and myosin ATPase was evaluated under various pH levels within the physiological range and it reached a maximum value in a slightly acidic environment. These results suggest that ATP/ADP flux control by the CK system is more important at lower pH, corresponding to the physiological state of muscle fatigue.
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PMID:Substrate channelling in a creatine kinase system of rat skeletal muscle under various pH conditions. 1252 49

During exercise, intracellular homeostasis depends on the matching of adenosine triphosphate (ATP) supply and ATP demand. Metabolites play a useful role in communicating the extent of ATP demand to the metabolic supply pathways. During fatigue from high-intensity exercise, a major change in the intracellular milieu of skeletal muscle is not ATP depletion but metabolite accumulation that affects the actomyosin cross-bridge interaction. The resulting reduction in myosin ATPase activity, cross-bridge turnover rate, and velocity of contraction can be considered a useful downregulation of ATP demand. Although maximal force is reduced, it is reduced less than myosin ATPase activity. In combination, efficiency of force production at the cross-bridge is thus enhanced. This is a second useful role for metabolites during fatigue because the total ATP cost per unit of force is partially reduced. Theoretical models predict that ADP may alleviate some effects of fatigue by further enhancing cross-bridge efficiency, thus providing a third useful role for metabolite accumulation. Recent experimental evidence reviewed here suggests that this occurs when ATP concentration is dramatically reduced. Single-fiber chemical analyses of fatigued muscle show lower ATP concentrations than other methods, but whether the appropriate microenvironments for effective competition by ADP for the nucleotide binding site occur around some or all of the cross-bridges remains technically difficult to prove at this time. During fatigue, muscle activation is also decreased, a response that potentially has the greatest effect on ATP demand-supply matching. I propose that the mismatch between the expected force production relative to muscle activation and the reduced force production from inorganic phosphate accumulation is the peripheral signal for reduced activation and is therefore the fourth useful role of metabolites in alleviating fatigue.
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PMID:Can any metabolites partially alleviate fatigue manifestations at the cross-bridge? 1470 63

Throat fan (dewlap) extension is sexually dimorphic in green anole lizards (Anolis carolinensis). Males have larger dewlaps which they display more frequently than females. Correlated with the behavior, sexual dimorphisms occur in the skeletal, muscular and neural structures responsible for dewlap extension in green anoles. We used histochemical techniques to stain for myosin ATPase and succinate dehydrogenase (SDH) to determine whether sex differences also exist in fiber type composition of the ceratohyoideus, the muscle that extends the dewlap. Based on the staining pattern for the two enzymes, four fiber types were identified: fast-oxidative-glycolytic (FOG), fast-glycolytic (FG), slow-oxidative (SO), and tonic. In the ceratohyoideus of both sexes, the predominate fiber types were FOG (approximately 43%) and FG (approximately 34%). Also in both males and females, the FOG and FG fibers had approximately twice the cross-sectional area of the SO and tonic fibers. No sex differences occurred in the percentages of FOG and FG fibers. However, males had a greater percentage of tonic fibers than females, whereas females had a greater percentage of SO fibers than males. The high proportion of FOG fibers in the anole ceratohyoideus makes it similar to other relatively fatigue-resistant muscles used in movements of moderate speed and duration. Although the precise role of tonic fibers in dewlap extension is not known, the greater percentage of these fibers in the male ceratohyoideus might be required to stabilize or maintain extension of the large dewlap apparatus in males.
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PMID:Fiber type composition of the muscle responsible for throat fan extension in green anole lizards. 1505 65

The larynx and its muscles are important for ventilation, coughing, sneezing, swallowing, Valsalva's maneuver, and phonation. Because of their functional demands, the intrinsic laryngeal muscles have a unique phenotype: very small and fast fibers with high mitochondrial content. How aging affects their function is largely unknown. In this study, we tested the hypothesis that an intrinsic laryngeal muscle (thyroarytenoid muscle, a vocal fold adductor) would become weaker, slower, and fatigable with age. Muscles from Fischer 344 x Brown Norway F1 hybrid rats (6, 18, and 30 mo of age) were used for in vitro contractile function and histology. Thyroarytenoid muscles generated significantly lower twitch and tetanic forces at 30 mo vs. 6 and 18 mo. Maximal shortening velocity decreased by 20% at 30 mo (vs. 6 mo), and velocity of unloaded shortening was slower at 18 and 30 mo by 19 and 27% vs. 6 mo. There was no histochemical evidence of altered myosin ATPase activity at 18 or 30 mo of age. Fatigue resistance was significantly decreased at 18 and 30 mo. We also found abundant mitochondrial clusters and ragged red fibers in the muscles of 30-mo-old rats, and there was an age-related increase in glycogen-positive fibers. We conclude that rat thyroarytenoid muscles become weaker, slower, and more fatigable with age. These functional changes are not due to alterations in myosin ATPase activity, but a switch in the expression of myosin isoforms remains a possibility. Finally, the alterations in mitochondrial and glycogen content indicate a shift in the metabolic characteristics of these muscles with age.
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PMID:Contractile dysfunction and altered metabolic profile of the aging rat thyroarytenoid muscle. 1623 5

High-frequency stimulation of skeletal muscle has long been associated with ionic perturbations, resulting in the loss of membrane excitability, which may prevent action potential propagation and result in skeletal muscle fatigue. Associated with intense skeletal muscle contractions are large changes in muscle metabolites. However, the role of metabolites in the loss of muscle excitability is not clear. The metabolic state of isolated rat extensor digitorum longus muscles at 30 degrees C was manipulated by decreasing energy expenditure and thereby allowed investigation of the effects of energy conservation on skeletal muscle excitability. Muscle ATP utilization was reduced using a combination of the cross-bridge cycling blocker N-benzyl-p-toluene sulfonamide (BTS) and the SR Ca2+ release channel blocker Na-dantrolene, which reduce activity of the myosin ATPase and SR Ca2+-ATPase. Compared with control muscles, the resting metabolites ATP, phosphocreatine, creatine, and lactate, as well as the resting muscle excitability as measured by M-waves, were unaffected by treatment with BTS plus dantrolene. Following 20 or 30 s of continuous 60-Hz stimulation, BTS-plus-dantrolene-treated muscles showed a 25% lower ATP utilization compared with control muscles. Furthermore, the ability of muscles to maintain excitability during high-frequency stimulation was significantly improved in BTS-plus-dantrolene-treated muscles, indicating a strong link between metabolites, energetic state, and the excitability of the muscle.
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PMID:Energy conservation attenuates the loss of skeletal muscle excitability during intense contractions. 1709 Jul 54

ATP provides the energy in our muscles to generate force, through its use by myosin ATPases, and helps to terminate contraction by pumping Ca(2+) back into the sarcoplasmic reticulum, achieved by Ca(2+) ATPase. The capacity to use ATP through these mechanisms is sufficiently high enough so that muscles could quickly deplete ATP. However, this potentially catastrophic depletion is avoided. It has been proposed that ATP is preserved not only by the control of metabolic pathways providing ATP but also by the regulation of the processes that use ATP. Considering that contraction (i.e. myosin ATPase activity) is triggered by release of Ca(2+), the use of ATP can be attenuated by decreasing Ca(2+) release within each cell. A lower level of Ca(2+) release can be accomplished by control of membrane potential and by direct regulation of the ryanodine receptor (RyR, the Ca(2+) release channel in the terminal cisternae). These highly redundant control mechanisms provide an effective means by which ATP can be preserved at the cellular level, avoiding metabolic catastrophe. This Commentary will review some of the known mechanisms by which this regulation of Ca(2+) release and contractile response is achieved, demonstrating that skeletal muscle fatigue is a consequence of attenuation of contractile activation; a process that allows avoidance of metabolic catastrophe.
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PMID:Skeletal muscle fatigue--regulation of excitation-contraction coupling to avoid metabolic catastrophe. 2262 29

The failure to transmit neural action potentials (APs) into muscle APs is referred to as neuromuscular transmission failure (NTF). Although synaptic dysfunction occurs in a variety of neuromuscular diseases and impaired neurotransmission contributes to muscle fatigue, direct evaluation of neurotransmission by measurement of successfully transduced muscle APs is difficult due to the subsequent movements produced by muscle. Moreover, the voltage-gated sodium channel inhibitor used to study neurotransmitter release at the adult neuromuscular junction is ineffective in embryonic tissue, making it nearly impossible to precisely measure any aspect of neurotransmission in embryonic lethal mouse mutants. In this study we utilized 3-(N-butylethanimidoyl)-4-hydroxy-2H-chromen-2-one (BHC), previously identified in a small-molecule screen of skeletal muscle myosin inhibitors, to suppress movements without affecting membrane currents. In contrast to previously characterized drugs from this screen such as N-benzyl-p-toluene sulphonamide (BTS), which inhibit skeletal muscle myosin ATPase activity but also block neurotransmission, BHC selectively blocked nerve-evoked muscle contraction without affecting neurotransmitter release. This feature allowed a detailed characterization of neurotransmission in both embryonic and adult mice. In the presence of BHC, neural APs produced by tonic stimulation of the phrenic nerve at rates up to 20 Hz were successfully transmitted into muscle APs. At higher rates of phrenic nerve stimulation, NTF was observed. NTF was intermittent and characterized by successful muscle APs following failed ones, with the percentage of successfully transmitted muscle APs diminishing over time. Nerve stimulation rates that failed to produce NTF in the presence of BHC similarly failed to produce a loss of peak muscle fiber shortening, which was examined using a novel optical method of muscle fatigue, or a loss of peak cytosolic calcium transient intensity, examined in whole populations of muscle cells expressing the genetically-encoded calcium indicator GCaMP3. Most importantly, BHC allowed for the first time a detailed analysis of synaptic transmission, calcium signaling and fatigue in embryonic mice, such as in Vamp2 mutants reported here, that die before or at birth. Together, these studies illustrate the wide utility of BHC in allowing stable measurements of neuromuscular function.
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PMID:A Novel Striated Muscle-Specific Myosin-Blocking Drug for the Study of Neuromuscular Physiology. 2799 Jan 7


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