Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper we develop a theory for calculating the chemical energy liberation and heat production of a skeletal muscle subjected to an arbitrary history of stimulation, loading, and length variation. This theory is based on and complements the distribution-moment (DM) model of muscle [Zahalak and Ma, J. biomech. Engng 112, 52-62 (1990)]. The DM model is a mathematical approximation of the A. F. Huxley cross-bridge theory and represents a muscle in terms of five (normalized) state variables: A, the muscle length, c, the sarcoplasmic free calcium concentration, and Q0, Q1, Q2, the first three moments of the actin-myosin bond-distribution function (which, respectively, have macroscopic interpretations as the muscle stiffness, force, and elastic energy stored in the contractile tissue). From this model are derived two equations which predict the chemical energy liberation and heat production rates in terms of the five DM state variables, and which take account of the following factors: (1) phosphocreatine hydrolysis associated with cross-bridge cycling; (2) phosphocreatine hydrolysis associated with sarcoplasmic-reticulum pumping of calcium; (3) passive calcium flux across the sarcoplasmic-reticulum membrane; (4) calcium-troponin bonding; (5) cross-bridge bonding at zero strain; (6) cross-bridge strain energy; (7) tendon strain energy; and (8) external work. Using estimated parameters appropriate for a frog sartorius at 0 degree C, the energy rates are calculated for several experiments reported in the literature, and reasonable agreement is found between our model and the measurements. (The selected experiments are confined to the plateau of the isometric length-tension curve, although our theory admits arbitrary length variations.) The two most important contributions to the energy rates are phosphocreatine hydrolysis associated with cross-bridge cycling and with sarcoplasmic-reticulum calcium pumping, and these two contributions are approximately equal under tetanic, isometric, steady-state conditions. The contribution of the calcium flux across the electrochemical potential gradient at the sarcoplasmic-reticulum membrane was found to be small under all conditions examined, and can be neglected. Long-term fatigue and oxidative recovery effects are not included in this theory. Also not included is the so-called 'unexplained energy' presumably associated with reactions which have not yet been identified. Within these limitations our model defines clear quantitative interrelations between the activation, mechanics, and energetics in muscle, and permits rational estimates of the energy production to be calculated for arbitrary programs of muscular work.
 ...
PMID:A distribution-moment model of energetics in skeletal muscle. 849 84

Extracellular Ca2+ has been shown to be important for the normal function of the diaphragm. In this study we have examined the potential importance of Na(+)-Ca2+ exchange as a mechanism for Ca2+ influx during the contractile process by studying the effect of inhibition or stimulation of Na(+)-Ca2+ exchange. Blockade of Na(+)-Ca2+ exchange with amiloride attenuated the twitch response, altered the force-frequency response curve, and enhanced the development of fatigue. The effect of amiloride could be partially reversed by increasing the extracellular Ca2+ concentration. The ability of amiloride to decrease force was associated with decreased Ca2+ uptake by the diaphragm. Enhancing intracellular Na(+)-extracellular Ca2+ exchange by inhibiting the Na(+)-K+ pump significantly decreased the rate of the development of muscle fatigue (89%). The maximal inhibition of diaphragmatic force produced by the amiloride analogue benzamil, which possesses 10-fold greater selectivity for Na(+)-Ca2+ exchange, was not significantly different from that produced by amiloride (76.2 +/- 1.1%), with a concentration that decreased maximum force by 50% equal to 46 microM compared with 460 microM for amiloride. Both agents slowed the maximal rate of relaxation up to 90%. Benzamil elevated resting tension during continuous stimulation of the diaphragm at 0.15 Hz. The results suggest that Na(+)-Ca2+ exchange may have a role in the normal function of the diaphragm.
 ...
PMID:Effect of amiloride on diaphragmatic contractility: evidence of a role for Na(+)-Ca2+ exchange. 203 97

The site of exercise-induced muscle fatigue is suggested to be the muscle membrane, which includes the sarcolemma and T-tubule membrane; the excitability of the membrane is dependent on the membrane potential. Significant potassium flux from the intracellular space of contracting muscle may decrease the membrane potential to half its resting value. This is true for isolated muscle preparations as well as for the whole body exercise in humans. Specific K+ channels have been identified, that may account for the intracellular K+ loss. Calcium-sensitive K+ channels open when intracellular Ca2+ concentrations increase, as during excitation. ATP-sensitive K+ channels may be involved but may open only at ATP concentrations well below those attained at exhaustion. However, ATP may be compartmentalized and only the membrane-bound ATP concentration may be of significance. Ca2+ accumulation and ATP depletion cause cell destruction; these changes induce an increased K+ conductance, which may inactivate the membrane and consequently prevent tension development. It is hypothesized that such a safety mechanism is identical to the fatigue mechanism.
 ...
PMID:Role of exercise-induced potassium fluxes underlying muscle fatigue: a brief review. 205 40

1. Nifedipine (1.5-3.0 x 10(-5) M) potentiated the (sub)tetanic tension during 10-50 Hz indirect or direct stimulation of the rat diaphragm preparation; the twitch contractions were not potentiated. 2. The effect was antagonized in high Ca2+ (5-10 x normal) solutions. 3. A comparison with the twitch potentiators caffeine (1.0 x 10(-3) M), quinine (1.4 x 10(-5) M) and phenytoin (2.0 x 10(-5) M), showed that only phenytoin, a putative Ca-antagonist, caused a nifedipine-like frequency-dependent potentiation, indicating a Ca-antagonistic rather than an unspecific effect. 4. A similar (sub)tetanic potentiation was found in a K(+)-free solution. 5. The slow development of the potentiation during repetitive stimulation is in accordance with an effect on the slow Ca channels known to be present in mammalian skeletal muscle. 6. A delay of the fatigue-inducing accumulation of K+ in the T tubules, which may occur during a nifedipine-induced reduction of a Ca2(+)-stimulated K+ efflux, as well as in a K(+)-free solution, may explain the effect.
 ...
PMID:Selective potentiation of subtetanic and tetanic contractions by the calcium-channel antagonist nifedipine in the rat diaphragm preparation. 205 26

Skeletal muscle has an inherent biochemical phenotypic plasticity that provides the possibility for it to be remodeled into a "heart-like" muscle for use in cardiac-assist devices. The purpose of this study was to chronically stimulate skeletal muscle electrically to transform the biochemical capacities of the three major subcellular systems (i.e., metabolic, calcium regulating, and contractile) to resemble those of heart muscle. The latissimus dorsi muscle (LDM) of mongrel dogs weighing 22-27 kg was stimulated via the thoracodorsal nerve at 2 Hz for 6-8 wk. This stimulation protocol reduced the phosphorylase (glycogenolytic) and phosphofructokinase (glycolytic) activities by 70%. The aerobic (citrate synthase activity) and fatty acid oxidative (3-hydroxyacyl-CoA dehydrogenase activity) capacities were not significantly increased by chronic stimulation and remained at about one-fourth those in the canine heart. The calcium-dependent sarcoplasmic reticulum adenosinetriphosphatase (ATPase) activity in the microsomal fraction, which was sixfold greater in the nonstimulated LDM than in the heart, was reduced by electrical stimulation to a level similar to that of the dog heart. The contractile capacity was evaluated by determining the percentage of types I and II fibers, the myofibrillar ATPase activity, and the proportion of myosin isoforms. The transformed muscle was comprised of 93 +/- 2% type I fibers, a myofibrillar ATPase activity similar to that in heart with primarily a slow-twitch muscle myosin isoform. In conclusion, electrical stimulation of canine LDM at 2 Hz for 6-8 wk resulted in two of the three biochemical systems, which confer physiological expression and fatigue resistance to muscle being transformed to resemble those of the myocardium.
 ...
PMID:Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices. 214 Aug 28

The release of neurohormone is widely thought to be exocytotic, involving Ca2(+)-dependent fusion of secretory vesicles with the plasma membrane. The inaccessibility of most nerve ending has so far hampered direct time-resolved measurements of neuronal exocytosis in response to brief depolarization. By using 'whole-terminal' patch-clamp and circuit-analysis techniques to measure membrane capacitance, we have now monitored changes in the surface membrane area of individual nerve terminals isolated from the mammalian neurohypophysis. A single depolarizing pulse leading to Ca2+ entry through voltage-gated calcium channels, rapidly and reproducibly increases the membrane area by an amount corresponding to the fusion of 1-100 secretory vesicles. The magnitude of the capacitance increase depends not only on Ca2+ entry and buffering, but also on the pattern of stimulation revealing facilitation, fatigue and recovery of the release process.
 ...
PMID:Direct measurement of exocytosis and calcium currents in single vertebrate nerve terminals. 215 58

Maintenance of low coronary flow (1 ml/min) during 40 or 70 min of anoxia maintained function and prevented Ca2+ overload during reoxygenation in isolated rat hearts. In comparison, recovery from 40 min of global ischemia resulted in only 20% of preischemic function and an increase in end-diastolic pressure (LVEDP) to 39 mmHg. Reperfusion Ca2+ uptake rose from 0.6 to 10.2 mumol/g dry tissue. Intracellular Na+ (Nai+) increased from 13 to 61 mumol/g dry tissue after 40 min of global ischemia, but was unchanged in hearts with low flow anoxia. When glucose and pyruvate were omitted from buffer used for anoxic perfusion, recovery was only 15% of preanoxic values, LVEDP rose to 32 mmHg, and reperfusion Ca2+ uptake was 7.2 mumol/g dry. In addition, Nai+ increased (47.4 mumol/g dry tissue) and ATP was depleted (1.0 mumol/g dry tissue) in the absence of substrate. In anoxic hearts supplied substrate, Nai+ stayed low (12 mumol/g dry tissue) and ATP was preserved (11.6 mumol/g dry tissue). Addition of ouabain (100 or 200 microM) and provision of zero-K+ buffer increased Nai+ and resulted in impaired functional recovery, increased LVEDP, and greater reperfusion Ca2+ uptake. These interventions also decreased energy availability in anoxic hearts. To distinguish between effects of Na+ accumulation and ATP depletion, monensin, a Na+ ionophore, was added during low flow anoxia. Monensin increased Nai+, decreased functional recovery and increased reperfusion Ca2+ uptake in a dose-dependent manner (1-10 microM) without changing ATP content. These results suggested that reduction of Nai+ accumulation by maintenance of Na+, K+ pump activity was the major mechanism of the beneficial effects of low coronary flow on reperfusion injury.
 ...
PMID:Na+ accumulation increases Ca2+ overload and impairs function in anoxic rat heart. 215 54

The purpose of this investigation was to determine the effects of low extracellular calcium and calcium antagonists on skeletal muscle staircase and fatigue. Initial experiments revealed that, brief exposure (10 minutes) of single frog sartorius muscle to diltiazem, D-600 (5 and 30 microM) and low calcium Ringer's solution (LCR, calcium replaced by magnesium and EGTA) had little effect on isometric twitches evoked every 30 seconds. However, when stimulated at 1 per second for 15 minutes, the calcium antagonists significantly decreased the magnitude and time course of the staircase, whereas LCR decreased only the time course. Each experimental condition significantly increased the rate of fatigue while diltiazem and D-600 both increased the magnitude of fatigue. Following the stimulation period, caffeine (10 mM) elicited contractures from all muscles whereas high potassium (180 mM) elicited contractures from control muscles only. These results indicate that calcium channel antagonists depress the skeletal muscle staircase response. They also indicate that these compounds as well as LCR enhance the fatigue process. Extracellular calcium influx may therefore have some influence on skeletal muscle twitches during prolonged repetitive activity.
 ...
PMID:Effects of low calcium and calcium antagonists on skeletal muscle staircase and fatigue. 217 74

Various antihypertensive drugs reduce blood pressure by different mechanisms. In some instances, adverse reactions occur because of specific hemodynamic effects. Examples include syncope with alpha-blockade or vasodilator therapy; fatigue or exercise intolerance with the reduction in cardiac output following the use of beta-adrenergic inhibitors; edema, headaches, or dizziness with the use of vasodilators such as calcium entry blockers; renal failure in patients with renal artery stenosis or renal insufficiency following the use of ACE inhibitors; and marked hyponatremia with volume depletion following the use of diuretics, especially in elderly patients. In the majority of patients, however, blood pressure lowering can be achieved without significant adverse effects. Combining small doses of different agents with different hemodynamic actions often results in good blood pressure control and minimal reactions. Examples of these include diuretics and beta-adrenergic inhibitors, diuretics and ACE inhibitors, and beta-blockers and vasodilators.
 ...
PMID:Do different hemodynamic effects of antihypertensive drugs translate into different safety profiles? 220 Jun 92

The effects of N-methyl-D-aspartate (NMDA) on the free intracellular Ca2+ concentration [( Ca2+]i) and the energy state in superfused cerebral cortical slices have been studied using 19F- and 31P-nuclear magnetic resonance spectroscopy. [Ca2+]i was measured using the calcium indicator 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA). NMDA (10 microM) in the absence of extracellular Mg2+ caused the expected rise in [Ca2+]i but produced an impairment of the energy state: the phosphocreatine (PCr) content was decreased by 42%, and the Pi/PCr ratio was increased by 55%. There was no detectable change in ATP or free intracellular Mg2+ concentration. Increasing the NMDA concentration in the superfusing medium to 100 or 400 microM caused no further increase in [Ca2+]i or further decrease in PCr content, but the Pi/PCr ratio continued to rise. The impairment of the energy state preceded the effect on [Ca2+]i, and these changes were irreversible on return to control conditions. Repeating the experiments in the presence of 1.2 mM extracellular Mg2+ resulted in similar changes in the energy state, with no change in [Ca2+]i. The possibilities that the effects were due to membrane depolarisation or to the presence of 5FBAPTA within the tissues were eliminated. The results suggest that low concentrations (10 microM) of NMDA produce an impaired energy state independent of the presence of extracellular Mg2+ and that the decreased energy state is not due to the changes in [Ca2+]i, which are seen only in the absence of extracellular Mg2+.
 ...
PMID:Effects of N-methyl-D-aspartate on [Ca2+]i and the energy state in the brain by 19F- and 31P-nuclear magnetic resonance spectroscopy. 220 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>