Inactivation of human muscle Na<sup>+</sup>-K<sup>+</sup>-ATPase in vitro during prolonged exercise is increased with hypoxia

Sandiford, S; Green, Howard J.; Duhamel, Todd A.; Perco, Jennifer G.; Schertzer, Jonathan D.; Ouyang, J.

doi:10.1152/japplphysiol.01273.2003

Cited by 45 publications

(48 citation statements)

References 56 publications

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“…These findings suggest that the impairment in neuromuscular function, measured before and after the progressive exercise, is attributable to sites other than the sarcolemma. In this regard, our findings confirm our earlier research using a prolonged exercise protocol, namely that the neuromuscular deficit that occurs with Norm and Hypox cannot be explained by a failure in membrane excitability (50). The results of the current study indicate that although using a test protocol in hypoxia severely blunts power output, compromises V O 2 peak , disrupts energy homeostasis, and depresses Na ϩ and K ϩ membrane transport potential, membrane excitability does not appear to be limiting.…”

Section: Discussionsupporting

confidence: 89%

“…It is possible that a failure in membrane excitability secondary to reductions in maximal Na ϩ -K ϩ -ATPase activity may explain the lower mechanical PO and lower peak aerobic power observed in hypoxia compared with normoxia (46,47). Support for this possibility comes from a recent study published by our group in which we have shown a greater reduction in maximal Na ϩ -K ϩ -ATPase activity during prolonged submaximal exercise when performed in hypoxia compared with normoxia (50). Although, we could find no evidence for a greater impairment in neuromuscular function during submaximal exercise in hypoxia, such may not be the case with progressive exercise.…”

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confidence: 90%

“…Although, we could find no evidence for a greater impairment in neuromuscular function during submaximal exercise in hypoxia, such may not be the case with progressive exercise. In contrast to submaximal exercise where force levels and motor unit firing rates are relatively low and V O 2 and muscle energy homeostasis are well protected (24,50), the generation of increased forces needed to perform progressive exercise exaggerates the demands on membrane excitability and V O 2 requirements and, in the process, greatly elevates metabolic by-product accumulation in muscle (6,49).…”

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confidence: 99%

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Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia

Sandiford

Green

Duhamel

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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To investigate the effects of hypoxia and incremental exercise on muscle contractility, membrane excitability, and maximal Na+-K+-ATPase activity, 10 untrained volunteers (age = 20 ± 0.37 yr and weight = 80.0 ± 3.54 kg; ± SE) performed progressive cycle exercise to fatigue on two occasions: while breathing normal room air (Norm; FiO2 = 0.21) and while breathing a normobaric hypoxic gas mixture (Hypox; FiO2 = 0.14). Muscle samples extracted from the vastus lateralis before exercise and at fatigue were analyzed for maximal Na+-K+-ATPase (K+-stimulated 3-O-methylfluorescein phosphatase) activity in homogenates. A 32% reduction ( P < 0.05) in Na+-K+-ATPase activity was observed (90.9 ± 7.6 vs. 62.1 ± 6.4 nmol·mg protein−1·h−1) in Norm. At fatigue, the reductions in Hypox were not different (81 ± 5.6 vs. 57.2 ± 7.5 nmol·mg protein−1·h−1) from Norm. Measurement of quadriceps neuromuscular function, assessed before and after exercise, indicated a generalized reduction ( P < 0.05) in maximal voluntary contractile force (MVC) and in force elicited at all frequencies of stimulation (10, 20, 30, 50, and 100 Hz). In general, no differences were observed between Norm and Hypox. The properties of the compound action potential, amplitude, duration, and area, which represent the electomyographic response to a single, supramaximal stimulus, were not altered by exercise or oxygen condition when assessed both during and after the progressive cycle task. Progressive exercise, conducted in Hypox, results in an inhibition of Na+-K+-ATPase activity and reductions in MVC and force at different frequencies of stimulation; these results are not different from those observed with Norm. These changes occur in the absence of reductions in neuromuscular excitability.

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confidence: 89%

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confidence: 90%

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confidence: 99%

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Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia

Sandiford

Green

Duhamel

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…At near-maximum exercise intensities, however, cardiac output, limb blood flow, and arteriovenous O 2 difference may not be able to compensate for reduced O 2 delivery. These factors may explain why a previous study did not find an effect of hypoxia on muscle fatigue as a result of moderateintensity, submaximal whole body exercise (44).…”

Section: Eiah Contributes To Locomotor Muscle Fatiguementioning

confidence: 89%

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

Romer

Haverkamp²,

Lovering³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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126

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-The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O 2 uptake (V O2 peak) ϭ 56.4 Ϯ 2.8 ml⅐kg Ϫ1 ⅐min Ϫ1 ; mean Ϯ SE]. Subjects exercised on a cycle ergometer at Ն90% V O2 peak to exhaustion (13.2 Ϯ 0.8 min), during which time arterial O 2 saturation (SaO 2 ) fell from 97.7 Ϯ 0.1% at rest to 91.9 Ϯ 0.9% (range 84 -94%) at end exercise, primarily because of changes in blood pH (7.183 Ϯ 0.017) and body temperature (38.9 Ϯ 0.2°C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (FIO 2 ) ϭ 0.25-0.31] that prevented EIAH (Sa O 2 ϭ 97-99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz). Immediately after exercise at FI O 2 0.21, the mean force response across 1-100 Hz decreased 33 Ϯ 5% compared with only 15 Ϯ 5% when EIAH was prevented (P Ͻ 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at FIO 2 0.21 (SaO 2 ϭ 95.3 Ϯ 0.7%), the decrease in evoked force was exacerbated by 35% (P Ͻ 0.05) in response to further desaturation induced via FI O 2 0.17 (SaO 2 ϭ 87.8 Ϯ 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O 2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (Ϫ6 Ϯ 1% ⌬Sa O 2 from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism. magnetic stimulation; low-and high-frequency fatigue; quadriceps twitch force; voluntary activation; peripheral fatigue; central fatigue EXERCISE-INDUCED ARTERIAL HYPOXEMIA (EIAH), defined as a reduced arterial HbO 2 saturation below preexercise levels, occurs during sustained, heavy-intensity exercise to exhaustion in a significant number of healthy subjects (9). The desaturation is attributable primarily to a reduced arterial O 2 partial pressure (Pa O 2 ) in some highly fit subjects (17, 22, 52) or, more universally, to a rightward shift of the O 2 dissociation curve because of a time-and intensity-dependent metabolic acidosis and an increase in body temperature (42,50). EIAH has a detrimental effect on maximal O 2 uptake (V O 2 max ) (16, 41) and endurance exercise performance (36, 37).Multiple "peripheral" and "central" mechanisms have been proposed to explain how arterial hypoxemia limits endurance exercise performance. There is potential for reduced O 2 transport to cause limb muscle fatigue during heavy exercise via an effect of hypoxia on Ca 2ϩ uptake and Ca 2ϩ release by the sarcoplasmic reticulum (10). Changes in the intracellular environment may impair Ca 2ϩ cycling and other excitation/ contraction processes. Alternatively, an inability of the sarcolemma and T tubule to conduct repetitive action potentials may indirectly reduce Ca 2ϩ cycling. The possibility that such peripheral processes are involved in exercise limitation during hypoxemia is suggested by the finding that...

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“…With the exception of the tissue samples, all other procedures and measurements were performed during the 3-day exercise protocol. We have previously reported that providing exercise patterns and dietary habits are not substantially altered, a wide range of muscle cellular properties remain stable over a similar time frame (15,69).…”

Section: Experimental Conditionsmentioning

confidence: 99%

Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery

Green

Bombardier²,

Duhamel³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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AR, Ouyang J. Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery. Am J Physiol Regul Integr Comp Physiol 295: R1238 -R1250, 2008. First published July 23, 2008 doi:10.1152/ajpregu.00171.2008This study investigated the responses in substrate-and energy-based properties to repetitive days of prolonged submaximal exercise and recovery. Twelve untrained volunteers (V O 2peak ϭ 44.8 Ϯ 2.0 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 , mean Ϯ SE) cycled (ϳ60 V O2peak) on three consecutive days followed by 3 days of recovery. Tissue samples were extracted from the vastus lateralis both pre-and postexercise on day 1 (E1), day 3 (E3), and during recovery (R1, R2, R3) and were analyzed for changes in metabolism, substrate, and enzymatic and transporter responses. For the metabolic properties (mmol/kg Ϫ1 dry wt), exercise on E1 resulted in reductions (P Ͻ 0.05) in phosphocreatine (PCr; 80 Ϯ 1.9 vs. 41.2 Ϯ 3.0) and increases (P Ͻ 0.05) in inosine monophosphate (IMP; 0.13 Ϯ 0.01 vs. 0.61 Ϯ 0.2) and lactate (3.1 Ϯ 0.4 vs. 19.2 Ϯ 4.3). At E3, both IMP and lactate were lower (P Ͻ 0.05) during exercise. For the transporters, the experimental protocol resulted in a decrease (P Ͻ 0.05) in glucose transporter-1 (GLUT1; 29% by R1), an increase in GLUT4 (29% by E3), and increases (P Ͻ 0.05) for both monocarboxylate transporters (MCT) (for MCT1, 23% by R2 and for MCT4, 18% by R1). Of the mitochondrial and cytosolic enzyme activities examined, cytochrome c oxidase (COX), and hexokinase were both reduced (P Ͻ 0.05) by exercise at E1 and in the case of hexokinase and phosphorylase by exercise on E3. With the exception at COX, which was lower (P Ͻ 0.05) at R1, no differences in enzyme activities existed at rest between E, E3, and recovery days. Results suggest that the glucose and lactate transporters are among the earliest adaptive responses of substrate and metabolic properties studied to the sudden onset of regular lowintensity exercise. contractile activity; glucose; lactate; transporters; vastus lateralis; glycogen; energy metabolism; enzyme activity IN WORKING SKELETAL MUSCLE, regular submaximal contractile activity promotes a better matching between ATP supply and ATP utilization, resulting in less of a disturbance in phosphorylation potential, increased delivery of fuels, such as carbohydrate (CHO) to the metabolic pathways so as not to be limiting to pathway flux, and attenuation of the by-products of metabolism, such as lactic acid, thereby minimizing their potentially disruptive effects (38,39,46,56,68).It has also been reported that these altered responses depend on a series of adaptations that increase the abundance of a multitude of proteins and protein isoforms that are involved in oxidative phosphorylation (OXPHOS), substrate availability, and metabolic by-product management. The tighter metabolic coupling, as an example, has been attributed to the increase in the potential for OXPHOS, which is believed to occur as a result of increases in mitochondrial density and the maximal ac...

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Inactivation of human muscle Na⁺-K⁺-ATPase in vitro during prolonged exercise is increased with hypoxia

Cited by 45 publications

References 56 publications

Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia

Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery

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Inactivation of human muscle Na+-K+-ATPase in vitro during prolonged exercise is increased with hypoxia

Cited by 45 publications

References 56 publications

Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia

Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery

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Inactivation of human muscle Na⁺-K⁺-ATPase in vitro during prolonged exercise is increased with hypoxia