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

This study examined the effects of fatigue on the functional aspects of the contractile apparatus and sarcoplasmic reticulum (SR). Frog semitendinosus muscles were stimulated to fatigue, and skinned fibers or a homogenate fraction was prepared from both fatigued and rested contralateral muscles. In fatigued fibers, maximal Ca2+-activated force of the contractile apparatus was unaltered, whereas maximal actomyosin-ATPase activity was depressed by 20%. The Ca2+ sensitivity of force was increased, whereas that of actomyosin-ATPase was not altered. Also, the rate constant for tension redevelopment was decreased at submaximal Ca2+ concentration. These latter findings suggest that fatigue slows the dissociation of force-generating myosin cross bridges. Ca2+ uptake and Ca2+-ATPase activity of the SR were depressed by 46 and 21%, respectively, in the fatigued muscles. Fatigue also reduced the rates of SR Ca2+ release evoked by AgNO3 and 4-chloro-m-cresol by 38 and 45%, respectively. During fatigue, the contractile apparatus and SR undergo intrinsic functional alterations. These changes likely result in altered force production and energy consumption by the intact muscle.
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PMID:Functional aspects of skeletal muscle contractile apparatus and sarcoplasmic reticulum after fatigue. 968 40

Sarcoplasmic reticulum (SR) responses to repeated sprints and to physical conditioning were studied in 10 Quarter Horses. Exercise tests (four repeated sprints on a treadmill) were conducted before and after 12 wk of sprint conditioning. Muscle samples from the middle gluteal muscle were taken before and after each exercise test, and SR vesicles were isolated. Calcium uptake was determined spectrophotometrically using antipyrylazo III, and Ca2+-ATPase activity was determined using an enzyme-linked optical assay. Conditioning increased calcium uptake rate and Ca2+-ATPase activity by 14 and 38%, respectively, before exercise and by 25 and 26% after exercise. Exercise decreased calcium uptake rate and Ca2+-ATPase activity by 37 and 27%, respectively, before conditioning and by 28 and 21% after conditioning. Decreases in calcium uptake and Ca2+-ATPase activity of SR have been associated with fatigue during exercise, and this association is strengthened by the moderating effect of conditioning.
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PMID:Sarcoplasmic reticulum responses to repeated sprints are affected by conditioning of horses. 992 11

1. This study examined the alterations in calcium release, calcium uptake and calcium ATPase activity of skeletal muscle sarcoplasmic reticulum in response to a bout of intense dynamic knee extensor exercise, and the relationship between these changes and alterations in muscle contractile characteristics in the human quadriceps. 2. In biopsy samples taken from the vastus lateralis, sarcoplasmic reticulum calcium release and calcium uptake were significantly depressed (P < 0.01 and 0.05, respectively) immediately following the exercise with no alteration in the sarcoplasmic reticulum Ca2+-ATPase activity. 3. A 33 % reduction in the maximum voluntary isometric torque was found following the exercise, with reduced torques from electrically evoked isometric contractions at low frequencies of stimulation (10 and 20 Hz) but not at higher frequencies (50 and 100 Hz). 4. The depressed calcium release was correlated (P < 0.05) with a decreased ratio of torques generated at 20:50 Hz, indicating an involvement in low frequency fatigue; however, no correlations between the muscle relaxation times or rates of change of torque and calcium uptake were observed.
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PMID:Sarcoplasmic reticulum function and muscle contractile character following fatiguing exercise in humans. 1125 Oct 66

Previous studies have shown that nuclear calcium signals control a variety of nuclear functions including gene transcription, DNA synthesis, DNA repair and nuclear envelope breakdown. The present study tested the hypothesis that the activity of the neuronal nuclear high affinity Ca2+-ATPase increases as a function of decreased energy metabolism in the cerebral cortex. Studies were performed in 11 ventilated newborn piglets, age 3-5 days, divided into normoxic (Nx, n = 4) and hypoxic (Hx, n = 7) groups. The animals were exposed to a single FiO2 in the range from 0.21 to 0.05 for one hr. Cerebral tissue hypoxia was confirmed biochemically by determining brain tissue ATP and phosphocreatine levels. Neuronal nuclei were isolated and the high-affinity Ca2+-ATPase activity determined. During graded hypoxia, cerebral tissue ATP decreased from 4.80 +/- 0.58 (normoxic) to 1.03 +/- 0.38 (ranging from 0.61-1.63) micromol/g brain (p < 0.05) and PCr decreased from 3.94 +/- 0.75 (normoxic) to 0.99 +/- 0.27 (ranging from 0.50 to 1.31) micromol/g brain (p < 0.05). The total high affinity Ca2+-ATPase activity in the hypoxic nuclei increased and ranged from 541 to 662 nmol/mg protein/hr, compared to activity in normoxic group of 327 to 446 nmol/mg protein/hr. During graded hypoxia, the level of nuclear high affinity Ca2+-ATPase activity correlated inversely with ATP (r = 0.91) and PCr levels (r = 0.82), with activity increasing as tissue high energy phosphates decreased. The results demonstrate that the decrease in cerebral energy metabolism during hypoxia is linearly correlated with an increase in activity of high affinity Ca2+-ATPase in cerebral cortical nuclei from immature brain. We propose that increased nuclear membrane high affinity Ca2+-ATPase activity, leading to increased nuclear Ca2+, will result in altered expression of apoptotic genes that could initiate programmed neuronal death.
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PMID:Effect of graded hypoxia on high-affinity Ca2+-ATPase activity in cortical neuronal nuclei of newborn piglets. 1188 86

This study uses genetically altered mice to examine the contribution of the Na(+)-K(+)-ATPase alpha2 catalytic subunit to resting potential, excitability, and contractility of the perinatal diaphragm. The alpha2 protein is reduced by 38% in alpha2-heterozygous and absent in alpha2-knockout mice, and alpha1-isoform is upregulated 1.9-fold in alpha2-knockout. Resting potentials are depolarized by 0.8-4.0 mV in heterozygous and knockout mice. Action potential threshold, overshoot, and duration are normal. Spontaneous firing, a developmental function, is impaired in knockout diaphragm, but this does not compromise its ability to fire evoked action potential trains, the dominant mode of activation near birth. Maximum tetanic force, rate of activation, force-frequency and force-voltage relationships, and onset and magnitude of fatigue are not changed. The major phenotypic consequence of reduced alpha2 content is that relaxation from contraction is 1.7-fold faster. This finding reveals a distinct cellular role of the alpha2-isoform at a step after membrane excitation, which cannot be restored simply by increasing alpha1 content. Na+/Ca2+ exchanger expression decreases in parallel with alpha2-isoform, suggesting that Ca2+ extrusion is affected by the altered alpha2 genotype. There are no major compensatory changes in expression of sarcoplasmic reticulum Ca(2+)-ATPase, phospholamban, or plasma membrane Ca(2+)-ATPase. These results demonstrate that the Na(+)-K(+)-ATPase alpha1-isoform alone is able to maintain equilibrium K+ and Na+ gradients and to substitute for alpha2-isoform in most cellular functions related to excitability and force. They further indicate that the alpha2-isoform contributes significantly less at rest than expected from its proportional content but can modulate contractility during muscle contraction.
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PMID:The Na(+)-K(+)-ATPase alpha2-subunit isoform modulates contractility in the perinatal mouse diaphragm. 1525 93

Chronic low-frequency stimulation of rabbit tibialis anterior muscle over a 24-h period induces a conspicuous loss of isometric tension that is unrelated to muscle energy metabolism (J.A. Cadefau, J. Parra, R. Cusso, G. Heine, D. Pette, Responses of fatigable and fatigue-resistant fibres of rabbit muscle to low-frequency stimulation, Pflugers Arch. 424 (1993) 529-537). To assess the involvement of sarcoplasmic reticulum and transverse tubular system in this force impairment, we isolated microsomal fractions from stimulated and control (contralateral, unstimulated) muscles on discontinuous sucrose gradients (27-32-34-38-45%, wt/wt). All the fractions were characterized in terms of calcium content, Ca2+/Mg2+-ATPase activity, and radioligand binding of [3H]-PN 200-110 and [3H]ryanodine, specific to dihydropyridine-sensitive calcium channels and ryanodine receptors, respectively. Gradient fractions of muscles stimulated for 24 h underwent acute changes in the pattern of protein bands. First, light fractions from longitudinal sarcoplasmic reticulum, enriched in Ca2+-ATPase activity, R1 and R2, were greatly reduced (67% and 51%, respectively); this reduction was reflected in protein yield of crude microsomal fractions prior to gradient loading (25%). Second, heavy fractions from the sarcoplasmic reticulum were modified, and part (52%) of the R3 fraction was shifted to the R4 fraction, which appeared as a thick, clotted band. Quantification of [3H]-PN 200-110 and [3H]-ryanodine binding revealed co-migration of terminal cisternae and t-tubules from R3 to R4, indicating the presence of triads. This density change may be associated with calcium overload of the sarcoplasmic reticulum, since total calcium rose three- to fourfold in stimulated muscle homogenates. These changes correlate well with ultrastructural damage to longitudinal sarcoplasmic reticulum and swelling of t-tubules revealed by electron microscopy. The ultrastructural changes observed here reflect exercise-induced damage of membrane systems that might severely compromise muscle function. Since this process is reversible, we suggest that it may be part of a physiological response to fatigue.
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PMID:Disturbances of the sarcoplasmic reticulum and transverse tubular system in 24-h electrostimulated fast-twitch skeletal muscle. 1567 Jul 32

Physiological and biochemical responses of skeletal muscle fibres to enhanced neuromuscular activity under conditions of maximum activation can be studied experimentally by chronic low-frequency stimulation of fast muscles. Stimulation-induced changes in the expression pattern of the rabbit fast skeletal muscle proteome were evaluated by two-dimensional gel electrophoresis and compared to the altered isoform expression profile of established transformation markers such as the Ca2+-ATPase, calsequestrin and the myosin heavy chain. Sixteen muscle proteins exhibited a marked change in their expression level. This included albumin with a 4-fold increase in abundance. In contrast, glycolytic enzymes, such as enolase and aldolase, showed a decreased expression. Concomitant changes were observed with marker elements of the contractile apparatus. While the fast isoforms of troponin T and myosin light chain 2 were drastically down-regulated, their slow counterparts exhibited increased expression. Interestingly, mitochondrial creatine kinase expression increased while the cytosolic isoform of this key muscle enzyme decreased. The expression of the small heat shock protein HSP-B5/alphaB-crystallin and the oxygen carrier protein myoglobin were both increased 2-fold following stimulation. The observed changes indicate that the conversion into fatigue-resistant red fibres depends on: (i) the optimum utilization of free fatty acids via albumin transportation, (ii) a rearrangement of the creatine kinase isozyme pattern for enhanced mitochondrial activity, (iii) an increased availability of oxygen for aerobic metabolism via myoglobin transport, (iv) the conversion of the contractile apparatus to isoforms with slower twitch characteristics and (v) the up-regulation of chaperone-like proteins for stabilising myofibrillar components during the fast-to-slow transition process.
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PMID:Differential expression of the fast skeletal muscle proteome following chronic low-frequency stimulation. 1614 47

The hypothesis tested was that disturbances in the sarcoplasmic reticulum (SR) Ca2+-cycling responses to exercise would associate with muscle glycogen reserves. Ten untrained males [peak O2 consumption (VO2 peak) = 3.41 +/- 0.20 (SE) l/min] performed a standardized cycle test (approximately 70% VO2 peak) on two occasions, namely, following 4 days of a high (Hi CHO)- and 4 days of a low (Lo CHO)-carbohydrate diet. Both Hi CHO and Lo CHO were preceded by a session of prolonged exercise designed to deplete muscle glycogen. SR Ca2+ cycling in crude homogenates prepared from vastus lateralis samples indicated higher (P < 0.05) Ca2+ uptake (microM x g protein(-1) x min(-1)) in Hi CHO compared with Lo CHO at 30 min (2.93 +/- 0.10 vs. 2.23 +/- 0.12) and at 67 min (2.77 +/- 0.16 vs. 2.10 +/- 0.12) of exercise, the point of fatigue in Lo CHO. Similar effects (P < 0.05) were noted between conditions for maximal Ca2+-ATPase (microM x g protein(-1) x min(-1)) at 30 min (142 +/- 8.5 vs. 107 +/- 5.0) and at 67 min (130 +/- 4.5 vs. 101 +/- 4.7). Both phase 1 and phase 2 Ca2+ release were 23 and 37% higher (P < 0.05) at 30 min of exercise and 15 and 34% higher (P < 0.05), at 67 min during Hi CHO compared with Lo CHO, respectively. No differences between conditions were observed at rest for any of these SR properties. Total muscle glycogen (mmol glucosyl units/kg dry wt) was higher (P < 0.05) in Hi CHO compared with Lo CHO at rest (+36%), 30 min (+53%), and at 67 min (+44%) of cycling. These results indicate that exercise-induced reductions in SR Ca2+-cycling properties occur earlier in exercise during low glycogen states compared with high glycogen states.
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PMID:Manipulation of dietary carbohydrates after prolonged effort modifies muscle sarcoplasmic reticulum responses in exercising males. 1669 Jul 65

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