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

We have used 31P nuclear magnetic resonance spectroscopy (31PNMRS) to study the relation between metabolism and contraction in frog skeletal muscle. Our results show a close association between [H2PO4(1-)] and both contractile and metabolic characteristics of muscle. We suggest that this metabolite links energy requiring to energy yielding function by participating in intermediate reactions which help to determine the rates of both processes. The observed relation between [H2PO4(1-)] and force production is consistent with the suggestion of Hibberd and colleagues, that Pi is reversibly released during the transition to the major force-producing actomyosin ATPase state. Our results also suggest that force fatigue is due to the buildup of the [H2PO4(1-)] product of ATP hydrolysis and that the effect of pH on force production is largely the result of altering H2PO4(1-)/HPO4(2-). We have found that it is the extent of glycogenolysis rather than the maximum activities of glycogenolytic enzymes that determines how much glycogen is broken down following anaerobic contraction. The most likely explanation for our results is that the ATP-forming reactions of glycolysis come to equilibrium during metabolic recovery from contraction under anaerobic conditions.
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PMID:The relation between muscle contraction and metabolism: studies by 31P nuclear magnetic resonance spectroscopy. 340 25

1. The rat lateral gastrocnemius muscle (LG) is a complex of four muscle compartments, each defined in terms of its unique innervation by a single primary nerve branch of the muscle nerve. A study has been made of the topographical distribution of motor units in the medial compartment of the LG (LGM) both before and after the loss of polyneuronal innervation that accompanies development. 2. Glycogen depletion methods showed that the distribution of single motor units depended on the rostro-caudal origins of their axons in the spinal cord: rostral axons possessed motor units almost exclusively confined to the medial half of the LGM; intermediate axons possessed motor units primarily in the intermediate and lateral part of the LGM; caudal axons possessed motor units that were not restricted to any particular part of the LGM. 3. Myosin ATPase staining showed that about 80% of the LGM consists of type II A fibres, whilst the remainder are type II B. Physiological determination of the contractile properties of motor units indicated two classes of units: those that were relatively fatigue resistant and did not show a sag property (like fast-twitch, fatigue-resistant fibres or FR) and those that were relatively fatigable and did show a sag property (like fast-twitch, fatigable fibres or FF). 4. Glycogen depletion was also used to determine the distribution of motor units in the LGM at 7 days post-natal, when most fibres still receive a polyneuronal innervation. The LGM primary nerve branch innervated a confined sub-volume of muscle fibres which is similar to the mature pattern. However, rostral axons possessed motor units that extended into the lateral half of the LGM, a position from which they are excluded in the adult. 5. These observations suggest that the axons of rostral and intermediate units form a topographical map within adult FR motor units (type II A fibres) in the LGM. The results suggest that competition between axon terminals for synaptic sites plays a role in the elimination of inappropriately positioned terminals and subsequent emergence of the topographical map.
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PMID:The formation of topographical maps in developing rat gastrocnemius muscle during synapse elimination. 341 2

Lactic acid is formed and accumulated in the muscle under conditions of high energy demand, rapid fluctuations of the energy requirement and insufficient supply of O2. During intense exercise sustained to fatigue muscle pH decreases to about 6.4-6.6. Force generation does not appear to be limited by the high H+ ion concentration per se but is more related to the PCr level. Phosphofructokinase may be inhibited by high H+ concentration but the inhibition is adequately overcome by increases in the activators AMP and ADP. A high concentration of H+ will decrease PCr by a direct effect on the creatine kinase equilibrium and indirectly by an increase in ADP. The effect of acidosis on glycolysis and on the PCr level will result in a decreased rate of ADP rephosphorylation, and it is suggested that ADP increases transiently above the steady-state level in the contracting muscle fibre. It is further suggested that the function of Na-K-ATPase is impaired by the increase of ADP resulting in an altered ionic balance over the muscle cell membrane. Muscle fatigue is thus considered to be due to an insufficient rate of ADP rephosphorylation resulting in a block in the activation process or in the excitation/contraction coupling.
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PMID:Muscle fatigue and lactic acid accumulation. 347 Oct 61

Muscle phosphorylase deficiency (McArdle's disease) has conventionally been considered a disorder of glycogenolysis, and the associated impairment in oxidative metabolism has been largely overlooked. Muscle glycogen normally is the primary oxidative fuel at exercise work loads requiring more than 75-80% of maximal O2 uptake (VO2max). Evidence is presented to support the hypothesis that a limited flux through the Embden-Myerhof pathway in McArdle's disease reduces the capacity to generate NADH required to support a normal VO2max. The extent of the oxidative defect is substrate dependent; i.e., it can be partially corrected by increasing the availability of alternative oxidative substrates (e.g., glucose, free fatty acids) to working muscle. Experiments employing modification of substrate availability closely link the hyperkinetic circulatory response to exercise (i.e., an abnormally large increase in O2 transport to skeletal muscle) and the premature muscle fatigue and cramping of McArdle patients with their oxidative impairment and suggest that a metabolic common denominator in these abnormal responses may be a pronounced decline in the muscle phosphorylation potential ([ATP]/[ADP][Pi]). The hyperkinetic circulation likely is mediated by the local effects on metabolically sensitive skeletal muscle afferents and vascular smooth muscle of K+, Pi, or adenosine or a combination of these substances released excessively from working skeletal muscle. The premature muscle fatigue and cramping of McArdle patients does not appear to be due to depletion of ATP but is associated with an increased accumulation of Pi and probably ADP in skeletal muscle. Accumulations of Pi and ADP are known to inhibit the myofibrillar, Ca2+, and Na+-K+-ATPase reactions.
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PMID:The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue. 352 13

During muscular fatigue two metabolites, hydrogen ions (H+) and inorganic phosphate (Pi), increase in concentration. The effect of increase in [H+] has been modeled mathematically for a system containing creatine kinase (EC 2.7.3.2), adenylate kinase (EC 2.7.4.3), and the appropriate concentrations of their substrates. Assuming that no other equilibrium reactions are involved, the result of acidification should be a useful increase in the ratio [ATP]/[ADP]. It is also shown by a reanalysis of earlier 31P NMR studies that the observed combination of increased [H+] and increased [Pi] leads to an increase in the monobasic phosphate concentration [Pi-] that is inversely proportional to the force of contraction. This suggests that Pi- may be a direct inhibitor of the actomyosin ATPase system.
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PMID:Muscular fatigue: effects of hydrogen ions and inorganic phosphate. 353 90

In the process of defining the recruitment of fuel and pathway selection in rainbow trout fast-twitch white skeletal muscle, it was clear that the near-maximal myosin adenosinetriphosphatase activity during a 10-s sprint was supported solely by phosphocreatine hydrolysis. A conservative estimate of the ATP turnover was 188 mumol X g wet wt-1 X min-1. It was not until the rate and force of contraction decreased that the relative contribution of anaerobic glycogenolysis became increasingly important. Over a 10-min period of burst swimming at approximately 120% of maximum aerobic steady-state swimming velocity of trout determined in a Brett-type swim tunnel, fatigue was associated with the near-depletion of glycogen in white muscle. The ATP turnover supported by anaerobic glycogenolysis was 78 mumol X g wet wt-1 X min-1. The glycolytic pathway appeared functional at this time with control sites being identified at hexokinase and phosphofructokinase (PFK-1). PFK-1 did not appear to be inhibited by low muscle pH (pH 6.66). In another exercise protocol lasting 30 min, complete exhaustion was related to glycogen depletion. The sum of all glycolytic intermediates from glucose 6-phosphate to pyruvate at exhaustion decreased by a dramatic 80% compared with the 25% decrease for the 10-min fatigue swimming protocol. This large depletion of glycolytic intermediates was accompanied by an 80% fall in ATP, a 70-80% reduction in the ATP/ADP and phosphorylation potential, and a 2.5-fold increase in the NAD/NADH. Associated with these changes was a marked displacement of the phosphoglycerate kinase (PGK), and the combined glyceraldehyde-3-phosphate dehydrogenase-PGK reactions from thermodynamic equilibrium. As a general conclusion, fatigue and exhaustion should be viewed as a multicomponent biochemical process in response to low glycogen and not leveled at one particular step of the glycolytic pathway.
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PMID:Regulation of anaerobic ATP-generating pathways in trout fast-twitch skeletal muscle. 360 83

The contractile properties of single motor units of rat plantaris were measured in situ 7 days following muscle partial denervation, achieved by section of radicular nerve L4. Partially denervated muscles weighed less, generated weaker twitch and tetanic forces, and contained denervated fibers, as evidenced by indirect/direct stimulation force ratios less than 1. Fast motor units (over 90% of unit pool) showed elevated twitch and tetanic responses (222% and 171% of controls, respectively) and elevated twitch-to-tetanic force ratios. Although partial denervation did not alter the mean fatiguability of fast motor units, fewer proportions of units remained in the extreme categories of fatigue resistance, with a clustering of units in the intermediate ranges. Slow units, while showing elevated twitch and tetanic responses, did not change in fatiguability. Glycogen depletion of the fibers of two fast motor units in partially denervated muscles revealed the presence of fibers varying in size, and in staining intensities for succinate dehydrogenase and ATPase, within the same motor unit, as a result of motoneurone sprouting.
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PMID:Force and fatiguability of sprouting motor units in partially denervated rat plantaris. 360 4

The hypothesis tested in this study was whether a skeletal muscle could be transformed to be fatigue resistant, to be used to power an implantable extra-aortic balloon assist device, and therefore to provide dynamically significant cardiac assistance. Eight dogs underwent implantation of an Itrel pacemaker to stimulate the thoracodorsal nerve over 8 to 18 weeks and transform the latissimus dorsi muscle. Biopsies of these muscles confirmed near complete (up to 98%) transformation into fatigue-resistance type I muscle fibers, identified by the adenosinetriphosphatase histochemical stains. Biochemical assays showed conversion of myosin isoforms to that of myocardial V3 phenotype, decreased activity of anaerobic glycolytic marker, and increased activity of aerobic enzyme marker, which indicated greater resemblance of such muscle to the myocardial fibers. In four dogs, the optimal stimulation parameters of such muscles in response to a burst stimulator, which synchronizes and summates the muscle contraction, were studied and compared with the contralateral, nontransformed muscle. Fatigue tests confirmed the marked fatigue resistance of the transformed muscle. In four dogs, a 100 ml balloon was placed beneath the transformed latissimus dorsi muscle and connected to the thoracic aorta with a Dacron graft. By means of the optimal burst-stimulating parameters identified above, the latissimus dorsi muscle was stimulated to contract during diastole, compressing the balloon to achieve diastolic augmentation while allowing the balloon to fill during systole. A 39% increase (p less than 0.001) in the "subendocardial viability index" (diastolic pressure-time index/tension-time index) was obtained as calculated from the left ventricular and ascending aortic pressure tracings. We conclude that the skeletal muscle can be transformed to resemble myocardium, which can generate sufficient force to provide hemodynamically significant and clinically relevant counterpulsation.
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PMID:Implantable extra-aortic balloon assist powered by transformed fatigue-resistant skeletal muscle. 366 97

This work tested whether the membrane electrical properties of cat motoneurons, the contractile properties of their muscle units, and the normal relationships among them would be restored 9 mo after section and resuture of their muscle nerve. Properties of medial gastrocnemius (MG) motor units were examined 9 mo following section and resuture of the MG nerve in adult cats. Motoneuron electrical properties and muscle-unit contractile properties were measured. Motor units were classified on the basis of their contractile properties as type fast twitch, fast fatiguing (FF), fast twitch with intermediate fatigue resistance (FI), fast twitch, fatigue resistant (FR), or slow twitch, fatigue resistant (S) (8, 20). Muscle fibers were classified as type fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) on the basis of histochemical staining for myosin adenosine triphosphatase, nicotinamide adenine dinucleotide diaphorase, and alpha-glycerophosphate dehydrogenase (48). Following 9 mo self-reinnervation, the proportions of each motor-unit type were the same as in normal control animals. Motoneuron membrane electrical properties [axonal conduction velocity, afterhyperpolarization (AHP) half-decay time, rheobase, and input resistance] also returned to control levels in those motoneurons that made functional reconnection with the muscle (as determined by ability to elicit measurable tension). The relationships among motoneuron electrical properties were normal in motoneurons making functional reconnection. Approximately 10% of MG motoneurons sampled did not elicit muscle contraction. These cells' membrane electrical properties were different from those that did elicit muscle contraction. Contractile speed and fatigue resistance of reinnervated muscle units had recovered to control levels at 9 mo postoperation. Force generation did not recover fully in type-FF units. The reduced tensions were apparently due to failure of recovery of FG muscle fiber area. Following reinnervation, relationships between motoneuron electrical and muscle-unit contractile properties were similar to controls. This was reflected in a degree of correspondence between motor-unit type and motoneuron type similar to normal units (84 vs. 86%, as defined by Ref. 61). There was a significantly increased proportion of type-SO muscle fibers and a decrease in the fast muscle fibers (especially type FOG) in 9 mo reinnervated MG. Together with the unchanged proportions of motor-unit types, this led to an estimate of average innervation ratios being increased in type-S motor units and decreased in type-FR units.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Properties of self-reinnervated motor units of medial gastrocnemius of cat. I. Long-term reinnervation. 371 73

Fatigue--or decrease in force generation--is a reduction of simultaneously attached cross-bridges in the force generating state. Two processes are necessary for the force generation: Firstly Ca++ release from the sarcoplasmic reticulum to the sarcoplasm and the binding of Ca++ by the troponin molecule and secondly the turnover of myosin-actin cross-bridges. These processes require energy in at least three different ATPase reactions and can consequently be inhibited when ATP hydrolysis is decreased, i.e. when ATP content is to low or when the reaction products (ADP, Pi and H+) reach inhibiting levels or when muscle pH has decreased to values inhibiting actomyosin ATPase activity (22). Low pH will also decrease Ca++ release and Ca++ affinity by troponin (23). In isometric contraction the force is well preserved as long as ADP phosphorylation can be provided by both PCr degradation and anaerobic glycolysis. When the PCr store is exhausted the force starts to decline and if muscle activation is maintained the force will continue to decrease along with falling glycolytic rate. ADP phosphorylation rate decreases successively and ATP content falls with an at least transient increase in ADP. The ATP decrease, apart from the minor increase in ADP, is balanced by an equimolar increase in IMP. Lactate accumulation produces an increasing acidity with muscle pH values down to 6.25. Early changes in free ADP content cannot be excluded as reason for the initial decrease in force production followed by more pronounced inhibition of ATPase activity during continued contraction due to both substrate lack and product inhibition together with pH effect on the excitation--contraction mechanism. In dynamic exercise with supramaximum work intensity the relation between fatigue development and metabolism is similar. In prolonged dynamic exercise relying on oxidative metabolism without lactate formation the point of fatigue is reached when the glycogen store is exhausted. Again ADP phosphorylation rate is decreased when the energy substrate is changed from carbohydrate to fat with lower maximum rate of ATP resynthesis.
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PMID:Biochemistry of muscle fatigue. 396 54


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