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

Biological and engineered motors are surprisingly similar in their adherence to two or possibly three fundamental regimes for the mass scaling of maximum force output (Fmax). One scaling regime (Group 1: myosin, kinesin, dynein and RNA polymerase molecules; muscle cells; whole muscles; winches; linear actuators) comprises motors that create slow translational motion with force outputs limited by the axial stress capacity of the motor, which results in Fmax scaling as motor mass0.67 (M0.67). Another scaling regime (Group 2: flying birds, bats and insects; swimming fish; running animals; piston engines; electric motors; jets) comprises motors that cycle rapidly, with significant internal and external accelerations, and for whom inertia and fatigue life appear to be important constraints. The scaling of inertial loads and fatigue life both appear to enforce Fmax scaling as M1.0 in these motors. Despite great differences in materials and mechanisms, the mass specific Fmax of Group 2 motors clusters tightly around a mean of 57 N kg(-1), a region of specific force loading where there appears to be a common transition from high- to low-cycle fatigue. For motors subject to multi-axial stresses, the steepness of the load-life curve in the neighborhood of 50-100 N kg(-1) may overwhelm other material and mechanistic factors, thereby homogenizing the mass specific Fmax of grossly dissimilar animals and machines. Rockets scale with Group 1 motors but for different mechanistic reasons; they are free from fatigue constraints and their thrust is determined by mass flow rates that depend on cross sectional area of the exit nozzle. There is possibly a third scaling regime of Fmax for small motors (bacterial and spermatazoan flagella; a protozoan spring) where viscosity dominates over inertia. Data for force output of viscous regime motors are scarce, but the few data available suggest a gradually increasing scaling slope that converges with the Group 2 scaling relationship at a Reynolds number of about 10(2). The Group 1 and Group 2 scaling relationships intersect at a motor mass of 4400 kg, which restricts the force output and design of Group 2 motors greater than this mass. Above 4400 kg, all motors are limited by stress and have Fmax that scales as M0.67; this results in a gradual decline in mass specific Fmax at motor mass greater than 4400 kg. Because of declining mass specific Fmax, there is little or no potential for biological or engineered motors or rockets larger than those already in use.
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PMID:Scaling of maximum net force output by motors used for locomotion. 1585 97

Alpha-sarcoglycan (Sgca) is a transmembrane glycoprotein of the dystrophin complex located at skeletal and cardiac muscle sarcolemma. Defects in the alpha-sarcoglycan gene (Sgca) cause the severe human-type 2D limb girdle muscular dystrophy. Because Sgca-null mice develop progressive muscular dystrophy similar to human disorder they are a valuable animal model for investigating the physiopathology of the disorder. In this study, biochemical and functional properties of fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of the Sgca-null mice were analyzed. EDL muscle of Sgca-null mice showed twitch and tetanic kinetics comparable with those of wild-type controls. In contrast, soleus muscle showed reduction of twitch half-relaxation time, prolongation of tetanic half-relaxation time, and increase of maximal rate of rise of tetanus. EDL muscle of Sgca-null mice demonstrated a marked reduction of specific twitch and tetanic tensions and a higher resistance to fatigue compared with controls, changes that were not evident in dystrophic soleus. Contrary to EDL fibers, soleus muscle fibers of Sgca-null mice distinctively showed right shift of the pCa-tension (pCa is the negative log of Ca2+ concentration) relationships and reduced sensitivity to caffeine of sarcoplasmic reticulum. Both EDL and soleus muscles showed striking changes in myosin heavy-chain (MHC) isoform composition, whereas EDL showed a larger number of hybrid fibers than soleus. In contrast to the EDL, soleus muscle of Sgca-null mice contained a higher number of regenerating fibers and thus higher levels of embryonic MHC. In conclusion, this study revealed profound distinctive biochemical and physiological modifications in fast- and slow-twitch muscles resulting from alpha-sarcoglycan deficiency.
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PMID:Deficiency of alpha-sarcoglycan differently affects fast- and slow-twitch skeletal muscles. 1600 56

We have previously reported our finding that IMP inhibits the Mg2+ -stimulated acto-myosin-ATPase activity of isolated actin and myosin. These experiments were undertaken at 35 degrees C and pH 7.0. It was also shown that the binding of actin to myosin was cooperative and that in the presence of IMP the Hill coefficient was decreased. The experiments shown here were carried out with isolated actin and myosin at three temperatures (25 degrees C, 31 degrees C and 37 degrees C) and three pH values (6, 7 and 8). The results show that: (i) the Mg2+ -stimulated acto-myosin-ATPase activity decreases with decreasing temperature; (ii) the Mg2+ -stimulated acto-myosin-ATPase activity is lower at pH = 6 and 8 compared to pH = 7; (iii) the effect of temperature and pH on the Mg2+ -stimulated acto-myosin-ATPase activity can be explained by a decrease in co-operativity between actin and myosin; (iv) IMP inhibits the Mg2+ -stimulated acto-myosin-ATPase activity at all temperatures and pH values. The greatest inhibition is found at pH = 7; and (v) the inhibition by pH + IMP is about the same for pH = 6 and pH = 7; at pH = 8 this combined inhibition is slightly higher. This leads to the same decrease in Mg2+ -stimulated acto-myosin-ATPase activity. Muscle fatigue can be explained by a combination of non-regulatory factors (for example pH) and regulatory factors (such as IMP) and from our results we conclude that IMP serves as an additional regulatory safety switch to maintain the balance between energy consumption and energy production and thereby preventing an energy crisis during exhaustive exercise of short duration.
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PMID:The effect of temperature and pH on the co-operative behavior of Mg2+ -stimulated acto-myosin-ATPase and the inhibition by IMP. 1602 36

The response of muscle to volitional or electrically induced stimuli is affected by its contractile history. Fatigue is the most obvious effect of contractile history reflected by the inability of a muscle to generate an expected level of force. However, fatigue can coexist with post-activation potentiation (PAP), which serves to improve muscular performance, especially in endurance exercise and activities involving speed and power. The measured response of muscular performance following some form of contractile activity is the net balance between processes that cause fatigue and the simultaneous processes that result in potentiation. Optimal performance occurs when fatigue has subsided but the potentiated effect still exists. PAP has been demonstrated using electrically induced twitch contractions and attributed to phosphorylation of myosin regulatory light chains, which makes actin and myosin more sensitive to Ca(2+). The potentiated state has also been attributed to an increase in alpha-motoneuron excitability as reflected by changes in the H-reflex. However, the significance of PAP to functional performance has not been well established. A number of recent studies have applied the principles of PAP to short-term motor performance as well as using it as a rationale for producing long-term neuromuscular changes through complex training. Complex training is a training strategy that involves the execution of a heavy resistance exercise (HRE) prior to performing an explosive movement with similar biomechanical characteristics, referred to as a complex pair. The complex pair is then repeated for a number of sets and postulated that over time will produce long-term changes in the ability of a muscle to generate power. The results of these studies are equivocal at this time and, in fact, no training studies have actually been undertaken. The discrepancies among the results of the various studies is due in part to differences in methodology and design, with particular reference to the mode and intensity of the HRE, the length of the rest interval within and between the complex pairs, the type of explosive activity, the training history of the participants, and the nature of the dependent variables. In addition, few of the applied studies have actually included measures of twitch response or H-reflex to determine if the muscles of interest are potentiated. There is clearly more research required in order to clarify the functional significance of PAP and, in particular, the efficacy of complex training in producing long-term neuromuscular adaptations.
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PMID:Post-activation potentiation: underlying physiology and implications for motor performance. 1602 72

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

Although everyone knows fatigue personally, it is a difficult concept to define. For muscular fatigue, one must know the aspect of performance affected. The most obvious demonstrations are decreased maximal force and slowed muscular answer. Fatigue can have a central origin, by reducing cognitive performance or lowering excitation of motoneurons. Various mediators are in question (serotonin, moduline, dopamine). The fatiguing muscular contractions are accompanied by reduced discharges of motoneurons. The neuromuscular junction does not seem to be in question. Cold reduces muscular power, whereas a hot environment limits exercise by a central mechanism, which starts the normal behavioural response to stop the exercise. Fatigue can also be the consequence of overtraining. In the periphery, the electric activity of the membrane's surface is the first possible sign of failure, which explains high-frequency fatigue: the accumulation of potassium outside the cell blocks the sodic channels to block the potentials of action or slow down their propagation. With fatigue, less calcium is released and limits the number of attached actin-myosin bridges connections of actin-myosin. The slowing down of the muscular answer represents a deterioration of the function of actin-myosin bridges. On the metabolic level, the most-often evoked changes are reduced pH and increased intracellular lactate level. However, these variations cannot all describe fatigue, since patients with Mc Ardle disease do not exhibit these variations but very quickly experience tiredness. In fact, an association of small metabolic intracellular variations could explain tiredness. The fast fibres are larger than slow fibres; their metabolic needs are higher and they are thus more sensitive to tiredness. The half time of recovery is within approximately 1 min: normal values of force and power are recovered after 5 to 10 min. During endurance activities, the limiting factors are glycogen reserves and levels of oxidative enzymes. On the whole, mechanisms of fatigue must be explored to completely understand the governing phenomena.
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PMID:Muscular fatigue. 1675 54

We have shown that myosin light chain phosphorylation inhibits fiber shortening velocity at high temperatures, 30 degrees C, in the presence of the phosphate analog vanadate. Vanadate inhibits tension by reversing the transition to force-generating states, thus mimicking a prepower stroke state. We have previously shown that at low temperatures vanadate also inhibits velocity, but at high temperatures it does not, with an abrupt transition in inhibition occurring near 25 degrees C (E. Pate, G. Wilson, M. Bhimani, and R. Cooke. Biophys J 66: 1554-1562, 1994). Here we show that for fibers activated in the presence of 0.5 mM vanadate, at 30 degrees C, shortening velocity is not inhibited in dephosphorylated fibers but is inhibited by 37 +/- 10% in fibers with phosphorylated myosin light chains. There is no effect of phosphorylation on fiber velocity in the presence of vanadate at 10 degrees C. The K(m) for ATP, defined by the maximum velocity of fibers partially inhibited by vanadate at 30 degrees C, is 20 +/- 4 microM for phosphorylated fibers and 192 +/- 40 microM for dephosphorylated fibers, showing that phosphorylation also affects the binding of ATP. Fiber stiffness is not affected by phosphorylation. Inhibition of velocity by phosphorylation at 30 degrees C depends on the phosphate analog, with approximately 12% inhibition in fibers activated in the presence of 5 mM BeF(3) and no inhibition in the presence of 0.25 mM AlF(4). Our results show that myosin phosphorylation can inhibit shortening velocity in fibers with large populations of myosin heads trapped in prepower stroke states, such as occurs during muscle fatigue.
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PMID:Myosin light chain phosphorylation inhibits muscle fiber shortening velocity in the presence of vanadate. 1715 67

During human locomotion the ability to generate and sustain mechanical power output is dependent on the organised variability in contractile and metabolic properties of the muscle fibres that comprise the active muscles. In studies of human exercise we have used a micro-dissection technique to obtain fragments of single muscle fibres from needle biopsies before and after exercise. Each fibre fragment is divided into two parts. One part is used to characterize the fibre type in respect of the heavy chain myosin isoform expressed. The other part of the fragment is analysed for high energy phosphate concentrations. Fibres are classified on the basis of expressing either type I, type IIA, or type IIX myosin heavy chain isoforms. It should be noted however that in the type II population many fibres co-express both IIA and the IIX isoforms and we therefore characterize these fibres on the basis of the degree of co-expression. We have used this technique to examine the time course of high energy phosphate concentration and fatigue in different fibre populations during exercise. The progressive reduction of power during maximal sprint efforts may be interpreted as the cumulative effect of metabolic depletion in successive fibre type populations from IIX to IIXa to IIAx to IIA to I. One important application of the micro-dissection technique is that PCr content may also be used as a very sensitive metabolic marker for fibre type recruitment during very short duration concentric, isometric and eccentric exercise.
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PMID:Human muscle fatigue: the significance of muscle fibre type variability studied using a micro-dissection approach. 1724 87

Inspiratory muscle weakness in patients with chronic obstructive pulmonary disease (COPD) is of major clinical relevance; maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered of pathologic nature. Although the fiber-type shift toward oxidative type I fibers in COPD diaphragm is regarded as beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single-fiber level is associated with loss of myosin content. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. The current Pulmonary Perspective postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force-generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients do not appear to be limited in their daily-life activities. Therefore, investigating in vivo diaphragm function in mild to moderate COPD should be the focus of future research. Treatment of diaphragm dysfunction in COPD is complex because its etiology is unclear, but recent findings show promise for the use of proteasome inhibitors in syndromes associated with muscle wasting, such as the diaphragm in COPD.
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PMID:Diaphragm muscle fiber dysfunction in chronic obstructive pulmonary disease: toward a pathophysiological concept. 1741 28

The hallmark of genetic CLC-1 chloride channel deficiency in myotonic humans, goats and mice is delayed muscle relaxation resulting from persistent electrical discharges. In addition to the ion channel defect, muscles from myotonic humans and mice also have major changes in fibre type and myosin isoform composition, but the extent to which this affects isometric contractions remains controversial. Many muscles, including the diaphragm, shorten considerably during normal activities, but shortening contractions have never been assessed in myotonic muscle. The present study tested the hypothesis that CLC-1 deficiency leads to an impairment of muscle isotonic contractile performance. This was tested in vitro on diaphragm muscle from SWR/J-Clcn1(adr-mto)/J myotonic mice. The CLC-1-deficient muscle demonstrated delayed relaxation, as expected. During the contractile phase, there were significant reductions in power and work across a number of stimulation frequencies and loads in CLC-1-deficient compared with normal muscle, the magnitude of which in many instances exceeded 50%. Reductions in shortening and velocity of shortening occurred, and were more pronounced when calculated as a function of absolute than relative load. However, the maximal unloaded shortening velocity calculated from Hill's equation was not altered significantly. The impaired isotonic contractile performance of CLC-1-deficient muscle persisted during fatigue-inducing stimulation. These data indicate that genetic CLC-1 chloride channel deficiency in mice not only produces myotonia but also substantially worsens the isotonic contractile performance of diaphragm muscle.
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PMID:Isotonic contractile impairment due to genetic CLC-1 chloride channel deficiency in myotonic mouse diaphragm muscle. 1748 99


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