ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.221000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Na+currents (INa) and membrane capacitance were studied with the loose patch voltage clamp technique and action potential properties were studied with a two‐electrode voltage clamp on the end‐plate, at the end‐plate border and on extrajunctional membrane of skeletal muscle fibres. Slow inactivation regulates the availableINaand is operative at the resting potential of both rat and human fibres. At the resting potential, slow inactivation causes a greater reduction inINain fast‐ than in slow‐twitch fibres. The relative resistance of slow‐twitch fibres to slow inactivation may enable slow‐twitch fibres to remain tonically active. Na+channel inactivation may provide a peripheral mechanism that limits the duration that fast‐twitch fibres can fire at high rates to prevent injury associated with prolonged high‐frequency contraction. Consequently, slow inactivation may enable fast‐twitch fibres to operate phasically at high rates or slow‐twitch fibres to fire continuously at lower rates. For both fast‐ and slow‐twitch fibres,INanormalized to membrane area was greatest on the end‐plate, intermediate on the end‐plate border and smallest on extrajunctional membrane. When normalized to membrane capacitance,INawas the same on the end‐plate and the end‐plate border and smallest on extrajunctional membrane. For a given membrane region,INawas larger on fast‐ than on slow‐twitch fibres. The higher density of Na+channels near the end‐plate increased the safety factor for neuromuscular transmission by lowering the action potential threshold and increasing the action

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.189000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The causative factors in muscle fatigue are multiple, and vary depending on the intensity and duration of the exercise, the fibre type composition of the muscle, and the individual's degree of fitness. Regardless of the aetiology, fatigue is characterized by the inability to maintain the required power output, and the decline in power can be attributed to a reduced force and velocity. Following high‐intensity exercise, peak force has been shown to recover biphasically with an initial rapid (2 min) recovery followed by a slower (50 min) return to the pre‐fatigued condition. The resting membrane potential depolarizes by 10–15 mV, while the action potential overshoot declines by a similar magnitude. Following high‐frequency stimulation of the frog semitendinous muscle, we observed intracellular potassium [K+]idecrease from 142±5 to 97±8 mm, while sodium [Na+]irose from 16±1 to 49±6 mm. The [K+]iloss was similar to that observed in fatigued mouse and human skeletal muscle, which suggests that there may be a limit to which [K+]ican decrease before the associated depolarization begins to limit the action potential frequency. Fibre depolarization to ‐60 mV (a value observed in some cells) caused a significant reduction in the t‐tubular charge movement, and the extent of the decline was inversely related to the concentration of extracellular Ca2+. A decrease in intracellular pH (pHi) to 6.0 was observed, and it has been suggested by some that low pH may disrupt E–C coupling by directly inhibiting the SR Ca2+release channel. However, Lambet al.(1992) observed that low pH had no effect on Ca2+release, and we found low pHito have no effect on t‐tubular charge movement (Q) or theQvs.Vmrelationship. The Ca2+released from the SR plays three important roles in the regulation of E–C coupling. As Ca2+rises, it binds to the inner surface of the t‐tubular charge sensor to increase charge (Qγ) and thus Ca2+release, it opens SR Ca2+channels that are not voltage‐regulated, and as [Ca2+]iincreases further it feeds back to close the same channels. The late stages of fatigue have been shown to be in part caused by a reduced SR Ca2+release. The exact cause of the reduced release is unknown, but the mechanism appears to involve a direct inhibi

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.191000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Fatigue and shortening‐induced deactivation, two conditions that both lead to reversible depression of the mechanical performance of striated muscle are briefly reviewed.Fatigue.Isolated fibres from frog skeletal muscle (1–3 °C) that are stimulated to produce a 1 s fused tetanus at 15 s intervals are brought into a state of reduced to 70–75% of the control) that is attributable to reduced performance of the myofibrils with no significant change in activation of the contractile system. A more intense stimulation programme (a single stimulus applied at 1–2 s intervals) reduces the tetanic force below 70% of the rested‐state level. Under these conditions, failure of activation becomes increasingly important as a cause of the force decline. Deficient inward spread of activation is likely to account for at least part of the force decline after a period of intense fatiguing stimulation.Shortening‐induced deactivation. Striated muscle that is allowed to shorten during activity loses some of its capacity to produce force, full restoration of the contractile strength being attained 1–2 s after the shortening phase. The depressant effect of shortening is demonstrable in skinned preparations as well as in intact muscle fibres and the magnitude of the effect is dependent on the state of activation of the muscle fibre when the movement occurs. The experimental evidence supports the view that sliding of the thick and thin filaments during activity reduces the affinity for calcium at the regulatory sites on the thin filament, leading to a transitory deactivation of the cont

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.t01-1-198000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

After a bout of intense exercise, especially in untrained persons, recovery of muscle force is often slow. Force depression is much more marked at low frequencies of stimulation than at high frequencies (recovery is also seen in single muscle fibres from frog and mouse after fatigue induced by repeated, brief contractions. Evidence from our own and other laboratories indicates that the impairment is unlikely to result from metabolic changes and points to a defect in excitation–contraction coupling. We demonstrate that the likely site of failure is in the coupling between t‐tubule depolarization and release of Ca2+from the SR. The causative agent appears to be a localized increase in cytoplasmic Ca2+which initiates some disruptive process, which can, however, be fully reversed, albeit slowly. Our experimental evidence does not support the involvement of Ca2+‐activated proteases. Attempts to clarify the possible role of Ca2+‐activated lipases (phospholipase A2) and Ca2+/calmodulin have been hampered by side‐effects of available inhibitors. Efforts to clarify how Ca2+exerts its effects are c

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.198000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The activity of ATP‐sensitive potassium channels of skeletal muscle is controlled by changes in the bioenergetic state of the cell. These channels are inactive in unfatigued muscle and become activated during fatigue. It has been postulated that ATP‐sensitive potassium channels shorten the action potential duration, increase the potassium efflux and contribute to the decrease in force during fatigue. Although blocking ATP‐sensitive potassium channels during fatigue prolongs the action potential duration and decreases the potassium efflux as expected, it does not affect the rate of fatigue development, as observed from the decrease in tetanic force. Even though such results are not consistent with the hypothesis that ATP‐sensitive potassium channels contribute to the decrease in force during fatigue, a reduced capacity of skeletal muscles to recover their tetanic force following fatigue is also observed when ATP‐sensitive potassium channels are blocked during fatigue, suggesting that these channels have a myoprotective effect. It is thus possible that removing this myoprotection during fatigue results in deleterious effects which counteract the expected slower decrease in force. However, ATP‐sensitive potassium channel openers also fail to affect the rate of fatigue development. Therefore, the results obtained so far do not support the hypothesis that ATP‐sensitive potassium channels contribute to the decrease in force d

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.210000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Since intracellular Na+activity (aiNa) is one important determinant of Na+, K+‐pump rate as well as excitability and the finely tuned contractility, it is surprising that the relation betweenaiNaand pump rate reported by different authors hask0.5varying between 10 and 40 mmol L‐1. Other data also point to a variable relation between pump rate andaiNa. During stimulation of isolated rat soleus muscles at 2 Hz, ouabain‐sensitive86Rb uptake was increased in spite of the intracellular Na+remaining unaltered. In isolated cardiomyocytes, a transient Na+, K+‐pump current was observed upon activation by extracellular K+in spite of good control ofaiNa. Na+‐loaded, isolated, sheep cardiac Purkinje fibres initially hyperpolarized over a period of up to 1 min upon activation of the Na+, K+pump with no detectable change ofaiNa. These examples are compatible with the existence of a micro‐environment close to the membrane where diffusion is slower than in the rest of the cytosol, so that localaiNamay fluctuate or gradients may develop as visualized by Wendt‐Gallitelliet al.(1993). We conclude that the reported relationships between Na+, K+‐pump rate andaiNain intact cells probably underestimate the true affinity of the Na+, K+pump for Na+due to a functional diffusion barrier beneath the sarcolemma, and also because of incomplete cell dialysis in whole‐cell voltage clamp experiments. The Na+, K+pump seems to be preferentially supplied with Na+from the outside through neighbouring channels

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.211000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

In skeletal muscle, the Na+, K+pump is predominantly situated in the sarcolemma (1000–3500 pumps per μm2). The total concentration can be determined in fresh or frozen biopsies (1–5 mg) using a3H‐ouabain binding assay. The values obtained have been confirmed by measurements of maximum ouabain suppressible Na+, K+‐transport capacity in intact muscles as well as Na+, K+‐ATPase‐related enzyme activity in muscle homogenates. In the mature organism, the concentration of Na+, K+pumps varies with muscle type and species in the range 150–600 pmol (g wet wt)‐1. In rat and human muscle, the concentration increases markedly with thyroid status. Semi‐starvation and untreated diabetes reduce the concentration by 20–48%. K+deficiency leads to a downregulation of up to 75%. Both in animals and in humans, training increases the concentration of Na+, K+pumps in muscle, and inactivity leads to a downregulation.High‐frequency stimulation elicits up to a 20‐fold increase in the net efflux of Na+within 10 s This is the major activation mechanism for the Na+, K+pump, utilizing its entire capacity and possibly represents a drive onde novosynthesis of Na+, K+pumps. A variety of hormones (insulin, insulin‐like growth factor I, adrenaline, noradrenaline, calcitonin gene‐related peptide, calcitonin, amylin) increase the rate of active Na+, K+transport by 60–120% within a few minutes. This leads to a decrease in intracellular Na+and hyperpolarization. In isolated muscles, where contractility is inhibited by high extracellular K+, such agents produce rapid force recovery, which is entirely suppressed by ouabain and closely correlated to the stimulation of K+uptake and the decline in intracellular Na+. The observations support the conclusion that the Na+, K+pump plays a central role in the acute recovery and maintenance of excitabili

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.209000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Skeletal muscles in an animal model of genetic hypertension (the spontaneously hypertensive rat, SHR) exhibit significant deficits in contractile performance. These deficits appear to be unrelated to the rise in blood pressure. Slow‐twitch soleus muscles show a decrease in specific muscle tension and a reduced resistance to muscle fatigue during prolonged contractile activity. We tested the hypothesis that the reduced fatigue resistance occurs as a consequence of an impaired ability to maintain or restore Na+and K+balance across the sarcolemma during repeated contractions. This may result from a genetically based increase in the Na+permeability of SHR muscles, coupled with a reduction Na+, K+pump capacity as the animals mature. Soleus muscles in adult SHR exhibit a significant increase in intracellular Na+content and a significant decrease in intracellular K+content at rest.86Rb+uptake in Na+‐loaded hypertensive muscles is 45% less than predicted from the number of ouabain‐binding sites available. Activation of Na+, K+pumps using adrenaline or insulin produces a significantly smaller hyperpolarization in hypertensive soleus than in control muscles. Control soleus muscles are hyperpolarized for at least 10 min after a 4 min period of high‐frequency activity, but hypertensive soleus muscles remain at resting polarity. Nonetheless, the number of ouabain‐binding sites in hypertensive muscles is significantly greater than in control soleus, and binding affinities are similar. This apparent deficit in pump capacity might lead to a greater and more prolonged increase in extracellular K+during repetitive contractions, and an associated decline in tension. Recently, we have been able to prevent the abnormal decrease in hypertensive soleus fatigue resistance by long‐term treatment (8 weeks) with the Ca2+blocker amlodipine. The therapy prevented or reversed the contractile deficits, but did not restore the responsiveness of the Na+, K+pump to hormonal stimulation. The current data suggest that both a reduction in Na+, K+‐pump capacity and changes in Ca2+distribution play a role in the development of contractile deficits in hyperte

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.195000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Intensive contractile activity is associated with a significant net loss of K+and a comparable gain of Na+in the working muscle fibres. This leads to an increase in the interstitial and T‐tubular K+concentration and to a decrease in the T‐tubular Na+concentration. It is well established that the exposure of muscles to high extracellular K+or low extracellular Na+inhibits contractile performance. More importantly, the combination of high extracellular K+and low extracellular Na+has a much more pronounced inhibitory effect on force than the sum of the individual effects of the two ions.The inhibitory effects of high extracellular K+or low extracellular Na+can be alleviated within 5–10 min by acute hormonal stimulation of the Na+, K+pump. In contrast, reductions in the capacity for active Na+, K+transport by pre‐incubation of isolated muscles with ouabain or by prior K+depletion of the animals significantly decreases contractile endurance during high‐frequency electrical stimulation. Thus, muscles from K+‐depleted rats exhibiting a 54% reduction in Na+, K+pump concentration showed a 110% increase in force decline during 30 s of 60 Hz stimulation. Reducing the Na+, K+pump capacity to a similar extent by pre‐incubation with ouabain led to a comparable decrease in endurance. Moreover, reductions in the Na+, K+pump capacity were associated with an increased intracellular accumulation of Na+during electrical stimulation. These observations support the notion that excitation‐induced decreases in Na+, K+gradients contribute to fatigue during intensive exercise and suggest that the capacity for active Na+, K+transport is a determining factor for contra

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.204000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY