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

The effects of the ATP-sensitive K+ channel (KATP channel) opener cromakalim on excitation-contraction (E-C) coupling were studied in skeletal muscle during fatiguing and non-fatiguing activity. Intracellular calcium concentration ([Ca2+]i) was monitored using the fluorescent indicator fura-2 in isolated single skeletal muscle fibres enzymatically dissociated from rat flexor digitorum brevis. A protocol of tetanic stimulation (50 Hz for 300 ms) with progressively shorter durations between tetani was used to induce E-C coupling failure in these cells. Cromakalim (100-800 microM) had little effect on peak [Ca2+]i during twitch and non-fatiguing tetanic stimulation. However, with 0.4 s between tetani, 100 microM cromakalim decreased peak tetanic [Ca2+]i from 1.47 +/- 0.11 microM to 8.35 +/- 55 nM, but did not affect resting [Ca2+]i (control, 220 +/- 40 nM; with cromakalim, 171 +/- 33 nM). Cyanide (2 mM) decreased tetanic [Ca2+]i and increased resting [Ca2+]i during the stimulus protocol; with 0.4 s between tetani, peak [Ca2+]i was 820 +/- 50 nM and resting [Ca2+]i was 443 +/- 32 nM. The ability of cromakalim to inhibit E-C coupling was enhanced by the presence of cyanide. Complete blockade of metabolism by cyanide and iodoactetate (0.1 mM) caused a marked rise in resting [Ca2+]i and inhibition of the tetanic rise of [Ca2+]i. With cromakalim (100 microM) present, E-C coupling failed during metabolic blockade but without a significant increase in resting [Ca2+]i. These results are consistent with a role for the KATP channel in the failure of Ca2+ release during fatigue.
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PMID:The effect of cromakalim on intracellular [Ca2+] in isolated rat skeletal muscle during fatigue and metabolic blockade. 917 67

Phasic and tonic motor neurons of crustaceans differ strikingly in their junctional synaptic physiology. Tonic neurons generally produce small excitatory postsynaptic potentials (EPSPs) that facilitate strongly as stimulation frequency is increased, and normally show no synaptic depression. In contrast, phasic neurons produce relatively large EPSPs with weak frequency facilitation and pronounced depression. We addressed the hypothesis that mitochondrial function is an important determinant of the features of synaptic transmission in these neurons. Mitochondrial fluorescence was measured with confocal microscopy in phasic and tonic axons and terminals of abdominal and leg muscles after exposure to supravital mitochondrial fluorochromes, rhodamine-123 (Rh123) and 4-diethylaminostyryl-N-methylpyridinium iodide (4-Di-2-Asp). Mitochondria of tonic axons and neuromuscular junctions had significantly higher mean Rh123 and 4-Di-2-Asp fluorescence than in phasic neurons, indicating more accumulation of the fluorochromes. Mitochondrial membrane potential, which is responsible for Rh123 uptake and is related to mitochondrial oxidative activity (the production of ATP by oxidation of metabolic substrates), is likely higher in tonic axons. Electron microscopy showed that tonic axons contain approximately fivefold more mitochondria per microm2 cross-sectional area than phasic axons. Neuromuscular junctions of tonic axons also have a much higher mitochondrial content than those of phasic axons. We tested the hypothesis that synaptic fatigue resistance is dependent on mitochondrial function in crayfish motor axons. Impairment of mitochondrial function by uncouplers of oxidative phosphorylation, dinitrophenol or carbonyl cyanide m-chlorophenylhydrazone, or by the electron transport inhibitor sodium azide, led to marked synaptic depression of a tonic axon and accelerated depression of a phasic axon during maintained stimulation. Iodoacetate, an inhibitor of glycolysis, and chloramphenicol, a mitochondrial protein synthesis inhibitor, had no significant effects on either mitochondrial fluorescence or synaptic depression in tonic or phasic axons. Collectively, the results provide evidence that mitochondrial oxidative metabolism is important for sustaining synaptic transmission during maintained stimulation of tonic and phasic motor neurons. Tonic neurons have a higher mitochondrial content and greater oxidative activity; these features are correlated with their greater resistance to synaptic depression. Conversely, phasic neurons have a lower mitochondrial content, less oxidative activity, and greater synaptic fatigability.
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PMID:Synaptic physiology and mitochondrial function in crayfish tonic and phasic motor neurons. 924 80

1. Intracellular calcium ([Ca2+]i) and tension were measured from single muscle fibres dissected from the cane toad (Bufo marinus). The amount of Ca2+ which could be released from the sarcoplasmic reticulum (SR) was estimated by brief (approximately 20 s) exposures to 4-chloro-m-cresol (4-CmC) or caffeine. 2. Muscle fatigue was produced by repeated tetani at 4 s or shorter intervals and continued until tension had fallen to 50% of the control. The intracellular free calcium concentration during a tetanus (tetanic [Ca2+]i) first increased and then steadily declined to 43+/-2% of control by the time tension had fallen to 50%. Over the period of fatigue the rapidly releasable Ca2+ from the SR fell to 46+/-6% of control. Tension and tetanic [Ca2+]i recovered to 93+/-3% and 100+/-4% of the control values after 20 min of rest. Over the same period rapidly releasable SR Ca2+ recovered to 98+/-12%. 3. When a similar number of tetani (200) were repeated at longer intervals (10 s), fibres showed only a small reduction in tension (to 85+/-1%) and tetanic [Ca2+]i did not change significantly. Under these conditions the rapidly releasable SR Ca2+ did not change significantly. 4. The recovery of rapidly releasable SR Ca2+ after fatigue was unaffected by removal of extracellular calcium but did not occur when oxidative phosphorylation was inhibited with cyanide. 5. These results suggest that an important cause of the decline of tetanic [Ca2+]i during fatigue is an equivalent decline in the amount of rapidly releasable SR Ca2+. The results show that the decline of rapidly releasable SR Ca2+ is related to a metabolic consequence of fatigue and are consistent with the hypothesis that Ca2+ precipitates with phosphate in the SR during fatigue.
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PMID:The role of calcium stores in fatigue of isolated single muscle fibres from the cane toad. 1043 47

The firefly luciferin/luciferase reaction was utilized to monitor intracellular ATP concentration ([ATP](i)). Single fibres of mouse skeletal muscle were dissected and injected with luciferase. Luciferin was added to the perfusate and light emission from the fibres was monitored as an indication of [ATP](i). Inhibition of oxidative phosphorylation with cyanide and anaerobic glycolysis with iodoacetate caused light emission to fall to zero within 10 min and the fibres developed a rigor contraction. Inhibition of creatine kinase with 2,4-dinitro-1-fluorobenzene produced a small transient fall in light emission in association with each tetanus. Muscle fibres were fatigued by repeated tetani and 5/12 fibres showed a fall in light emission in the late phase of fatigue. If fibres were allowed to recover from fatigue in the absence of glucose and then restimulated in the absence of glucose they fatigued much more rapidly. However, such fibres showed no obvious change in light emission. We conclude that the luciferin/luciferase system can be used to monitor [ATP](i) in functioning single skeletal muscle cells. A depletion of global [ATP](i) is not observed in all fatiguing fibres and cannot be the sole cause of the final phase of fatigue.
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PMID:Intracellular ATP measured with luciferin/luciferase in isolated single mouse skeletal muscle fibres. 1188 83

Previous studies on single fast-twitch fibres from mouse toe muscles have shown marked fatigue-induced changes in the free myoplasmic [Ca2+] ([Ca2+]i), while mitochondrial [Ca2+] remained unchanged. We have now investigated whether muscle fibres from the legs of mice respond in a similar way. Intact, single fibres were dissected from the soleus and extensor digitorum longus (EDL) muscles of adult mice. To measure [Ca2+]i, indo-1 was injected into the isolated fibres. Mitochondrial [Ca2+] was measured using Rhod-2 and confocal laser microscopy. Fatigue was induced by up to 1000 tetanic contractions (70 Hz) given at 2 s intervals. In soleus fibres, there was no significant decrease in tetanic [Ca2+]i at the end of the fatiguing stimulation, whereas tetanic force was significantly reduced by about 30 %. In 10 out of 14 soleus fibres loaded with Rhod-2 and subjected to fatigue, mitochondrial [Ca2+] increased to a maximum after about 50 tetani; this increase was fully reversed within 20 min after the end of stimulation. The force-frequency curve of the non-responding soleus fibres was shifted to higher frequencies compared to that of the responding fibres. In addition, eight out of nine Rhod-2-loaded EDL fibres showed similar changes in mitochondrial [Ca2+] during and after a period of fatiguing stimulation. The stimulation-induced increase in mitochondrial [Ca2+] was reduced when mitochondria were depolarised by application of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, whereas it was increased by application of an inhibitor of the mitochondrial Na+/Ca2+ exchange (CGP-37157). In conclusion, isolated slow-twitch muscle fibres show only modest changes in tetanic force and [Ca2+]i during repeated contractions. The increase in mitochondrial Ca2+ does not appear to be essential for activation of mitochondrial ATP production, nor does it cause muscle damage.
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PMID:Mitochondrial and myoplasmic [Ca2+] in single fibres from mouse limb muscles during repeated tetanic contractions. 1281 78

Creatine kinase (CK) has a central role in skeletal muscle, acting as a fast energy buffer and shuttle between sites of energy production (mitochondria) and consumption (cross-bridges and ion pumps). Unexpectedly, isolated fast-twitch skeletal muscle cells of mice deficient in both cytosolic and mitochondrial CK (CK-/-) are highly fatigue resistant during stimulation protocols that stress aerobic metabolism. We have now studied different aspects of mitochondrial function in CK-/- skeletal muscle. Intact, single fibres of flexor digitorum brevis (FDB) muscles were fatigued by repeated tetanic stimulation (70 Hz, 350 ms duration, duty cycle 0.14). Under control conditions, CK-/- FDB fibres were more fatigue resistant than wild-type fibres. However, after mitochondrial inhibition with cyanide, force declined markedly faster in CK-/- fibres than in wild-type fibres. The rapid force decline in CK-/- fibres was not due to decreased myoplasmic [Ca2+] during tetani (measured with indo-1), which in these fibres remained virtually constant during fatigue in the presence of cyanide. Intact, single fibres of highly oxidative soleus muscles were fatigued by repeated tetani (50 Hz, 500 ms duration, duty cycle 0.5). All CK-/- soleus fibres tested (n = 9) produced > 40 % force at the end of the fatiguing stimulation period (500 tetani), whereas force fell to < 40 % before 500 tetani in two of three wild-type fibres. Mitochondrial [Ca2+] (measured with rhod-2 and confocal microscopy) increased during repeated tetanic stimulation in CK-/- but not in wild-type FDB fibres. In conclusion, mitochondria and energy shuttling operate effectively in CK-/- fibres and this is associated with an increase in mitochondrial [Ca2+].
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PMID:Mitochondrial function in intact skeletal muscle fibres of creatine kinase deficient mice. 1456 23

Isolated whole skeletal muscles fatigue more rapidly than isolated single muscle fibres. We have now employed this difference to study mechanisms of skeletal muscle fatigue. Isolated whole soleus and extensor digitorum longus (EDL) muscles were fatigued by repeated tetanic stimulation while measuring force production. Neither application of 10 mm lactic acid nor increasing the [K(+)] of the bath solution from 5 to 10 mm had any significant effect on the rate of force decline during fatigue induced by repeated brief tetani. Soleus muscles fatigued slightly faster during continuous tetanic stimulation in 10 mm[K(+)]. Inhibition of mitochondrial respiration with cyanide resulted in a faster fatigue development in both soleus and EDL muscles. Single soleus muscle fibres were fatigued by repeated tetani while measuring force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)). Under control conditions, the single fibres were substantially more fatigue resistant than the whole soleus muscles; tetanic force at the end of a series of 100 tetani was reduced by about 10% and 50%, respectively. However, in the presence of cyanide, fatigue developed at a similar rate in whole muscles and single fibres, and tetanic force at the end of fatiguing stimulation was reduced by approximately 80%. The force decrease in the presence of cyanide was associated with a approximately 50% decrease in tetanic [Ca(2+)](i), compared with an increase of approximately 20% without cyanide. In conclusion, lactic acid or [K(+)] has little impact on fatigue induced by repeated tetani, whereas hypoxia speeds up fatigue development and this is mainly due to an impaired Ca(2+) release from the sarcoplasmic reticulum.
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PMID:Limited oxygen diffusion accelerates fatigue development in mouse skeletal muscle. 1645 85

We investigated the role of limitations in aerobic metabolism, glycolysis, and membrane excitability for development of high-frequency fatigue in isolated rat soleus muscle. Muscles mounted on force transducers were incubated in buffer bubbled with 5% CO(2) and either 95% O(2) (oxygenated) or 95% N(2) (anoxic) and stimulated at 60 Hz continuously for 30-120 s or intermittently for 120 s. Cyanide (2 mM) and 2-deoxyglucose (10 mM) were used to inhibit aerobic metabolism and both glycolysis and aerobic metabolism, respectively. Excitability was reduced by carbacholine (10 microM), a nicotinic ACh receptor agonist, or ouabain (10 microM), an Na(+)-K(+) pump inhibitor. Membrane excitability was measured by recording M waves. Intracellular Na(+) and K(+) contents and membrane potentials were measured by flame photometry and microelectrodes, respectively. During 120 s of continuous stimulation, oxygenated and anoxic muscles showed the same force loss. In oxygenated muscles, cyanide did not alter force loss for up to 90 s, whereas 2-deoxyglucose increased force loss (by 19-69%; P < 0.01) from 14 s of stimulation. In oxygenated muscles, 60 s of stimulation reduced force, M wave area, and amplitude by 70-90% (P < 0.001). Carbacholine or ouabain increased intracellular Na(+) content (P < 0.001), induced a 7- to 8-mV membrane depolarization (P < 0.001), and accelerated the rate of force loss (by 250-414%) during 30 s of stimulation (P < 0.001). Similar effects were seen with intermittent stimulation. In conclusion, limitations in glycolysis and subsequently also in aerobic metabolism, as well as membrane excitability but not aerobic metabolism alone, appear to play an important role in the development of high-frequency fatigue in isolated rat soleus muscle.
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PMID:The importance of limitations in aerobic metabolism, glycolysis, and membrane excitability for the development of high-frequency fatigue in isolated rat soleus muscle. 1723 55

In the afternoon of March 23, 2006 a Providence firefighter was diagnosed as having cyanide poisoning after working at a building fire. In the aftermath of three fires at commercial and residential sites that day, eight additional firefighters (out of 28 tested) were found to have elevated levels of cyanide. Numerous other members reported symptoms consistent with cyanide poisoning, including headaches, weakness and fatigue, nausea, and shortness of breath. The Providence Fire Department (PFD) established a joint union management committee to review the situation.
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PMID:Report of the investigation committee into the cyanide poisonings of Providence firefighters. 1837 73

Photochromic filter solutions have been developed for flash blindness protection. Triarylmethane leuconitriles, which dissociate into a colored dye cation and cyanide ion when activated by uv light, produce high closed densities and open transmission. The fading rate of the dye solutions can be controlled by the choice of solvent or bleach anion concentration. However, the closed density of these solutions decreases when repeatedly activated with a xenon flash. It has been found that this fatigue can be greatly reduced by substitution of bisulfite for cyanide as the triarylmethane counter ion. Triarylmethane bisulfite solutions retain up to 99% of the initial closed density after fifty xenon flashes. The temperature coefficient of fading of the leucobisulfites in aqueous methanol is much smaller than that of spiropyran solutions in toluene.
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PMID:Photochromic aminotriarylmethane solutions for flash blindness protection. 2007 13


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