Metabolic end products inhibit sarcoplasmic reticulum Ca2+ release and [3H]ryanodine binding

Favero, Terence G.; Zable, Anthony C.; Bowman, MA; Thompson, Ann D.; Abramson, Jonathan J.

doi:10.1152/jappl.1995.78.5.1665

Cited by 108 publications

(50 citation statements)

References 22 publications

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“…1 for review). Reduced substrate (i.e., ATP, glycogen) availability may reduce SR Ca 2ϩ release (11,23), and metabolic end products, such as H ϩ , lactate, and Mg 2ϩ , have been shown to reduce Ca 2ϩ release from SR vesicles (14), although the effect of increased H ϩ is not seen in skinned fiber preparations (19). Thus, the metabolic alterations resulting from the sprints may have impaired SR function and contributed to the reduced exercise performance we have observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Muscle metabolites and performance during high-intensity, intermittent exercise

Hargreaves

McKenna²,

Jenkins

et al. 1998

Journal of Applied Physiology

132

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. Muscle metabolites and performance during high-intensity, intermittent exercise. J. Appl. Physiol. 84(5): 1687-1691, 1998.-Six men were studied during four 30-s ''all-out'' exercise bouts on an air-braked cycle ergometer. The first three exercise bouts were separated by 4 min of passive recovery; after the third bout, subjects rested for 4 min, exercised for 30 min at 30-35% peak O 2 consumption, and rested for a further 60 min before completing the fourth exercise bout. Peak power and total work were reduced (P Ͻ 0.05) during bout 3 [765 Ϯ 60 (SE) W; 15.8 Ϯ 1.0 kJ] compared with bout 1 (1,168 Ϯ 55 W, 23.8 Ϯ 1.2 kJ), but no difference in exercise performance was observed between bouts 1 and 4 (1,094 Ϯ 64 W, 23.2 Ϯ 1.4 kJ). Before bout 3, muscle ATP, creatine phosphate (CP), glycogen, pH, and sarcoplasmic reticulum (SR) Ca 2ϩ uptake were reduced, while muscle lactate and inosine 5Ј-monophosphate were increased. Muscle ATP and glycogen before bout 4 remained lower than values before bout 1 (P Ͻ 0.05), but there were no differences in muscle inosine 5Ј-monophosphate, lactate, pH, and SR Ca 2ϩ uptake. Muscle CP levels before bout 4 had increased above resting levels. Consistent with the decline in muscle ATP were increases in hypoxanthine and inosine before bouts 3 and 4. The decline in exercise performance does not appear to be related to a reduction in muscle glycogen. Instead, it may be caused by reduced CP availability, increased H ϩ concentration, impairment in SR function, or some other fatigue-inducing agent. muscle fatigue; metabolism; glycogen; creatine phosphate; hydrogen ion DURING HIGH-INTENSITY EXERCISE, the major pathways for ATP resynthesis are the breakdown of creatine phosphate (CP) and the degradation of muscle glycogen to lactic acid (21,26,32). With repeated bouts of high-intensity exercise, the contribution of these processes to ATP turnover declines, and although there is an increase in the aerobic contribution to exercise (5, 26), reduced power output and total work production result (21,26). Reduced CP and glycogen availability may contribute to this decline in anaerobic energy production and exercise performance. Recently, a close relationship between CP availability and power output during intense exercise has been demonstrated (5, 6). Furthermore, intense knee extensor exercise performance during two exercise bouts separated by 1 h was maintained in a leg with elevated muscle glycogen, whereas performance was reduced in the contralateral leg with reduced muscle glycogen (3).Alternatively, it is possible that intramuscular acidosis, as a consequence of the increased glycolytic flux and electrolyte shifts that occur during intense exercise, is responsible for impaired performance. Increased hydrogen ion concentration ([H ϩ ]) may impair tension development (22) and/or reduce muscle glycogenolyis by inhibiting the activity of phosphofructokinase and/or phosphorylase (26). However, recent studies in humans have questioned the inhibitory effects of increased muscle acidity on muscle force pro...

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Section: Discussionmentioning

confidence: 99%

Muscle metabolites and performance during high-intensity, intermittent exercise

Hargreaves

McKenna²,

Jenkins

et al. 1998

Journal of Applied Physiology

132

View full text Add to dashboard Cite

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“…These, in turn, have been linked to several processes that contribute to fatigue, including the accelerated breakdown of creatine phosphate (McCann, Mollé, & Caton, 1995), the inhibition of glycolysis and glycogenolysis (Spriet, Lindinger, McKelvie, Heigenhauser, & Jones, 1989), the inhibition of lipolysis (Boyd, Giamber, Mager, & Lebovitz, 1974) and the interference with the calcium triggering of muscle contractions (Favero, Zable, Bowman, Thompson, & Abramson, 1995). In addition, lactic acidosis stimulates the release of catecholamines (Goldsmith, Iber, McArthur, & Davies, 1990), and thus the lactate threshold has been found to occur in close proximity to a catecholamine threshold (Urhausen, Weiler, Coen, & Kindermann, 1994;Weltman et al, 1994).…”

Section: Domain Of ''Heavy'' Intensitymentioning

confidence: 99%

Variation and homogeneity in affective responses to physical activity of varying intensities: An alternative perspective on dose – response based on evolutionary considerations

Ekkekakis

Hall

Petruzzello

2005

Journal of Sports Sciences

307

325

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A model for systematic changes in patterns of inter-individual variation in affective responses to physical activity of varying intensities is presented, as a conceptual alternative to the search for a global dose -response curve. It is theorized that trends towards universality will emerge in response to activities that are either generally adaptive, such as moderate walking, or generally maladaptive, such as strenuous running that requires anaerobic metabolism and precludes the maintenance of a physiological steady state. At the former intensity the dominant response will be pleasure, whereas at the latter intensity the dominant response will be displeasure. In contrast, affective responses will be highly variable, involving pleasure or displeasure, when the intensity of physical activity approximates the transition from aerobic to anaerobic metabolism, since activity performed at this intensity entails a trade-off between benefits and risks. Preliminary evidence in support of this model is presented, based on a reanalysis of data from a series of studies.

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“…Changes in expression of eNOS (also known as NOS1) have been reported, and skeletal muscle expression of iNOS (also known as NOS2) is elevated in heart failure (99). ROS and NO have been shown to modify RyR1 channel function (15,19,20,22) and are potentially implicated in the Ca 2+ handling defects in heart failure. Further studies are required to identify direct roles for ROS and NO in altering RyR1 function and inducing skeletal muscle dysfunction in heart failure.…”

Section: Figurementioning

confidence: 99%

“…Cysteine residues in RyR1 are S-nitrosylated, S-glutathionylated, or oxidized under distinct physiological conditions (18,19). It has been proposed that S-nitrosylation might, in some cases, protect against the inhibitory effects of oxidation (20,21). However, it remains to be determined precisely how posttranslational modifications of cysteine residues in RyR1 regulate the function of the channel in vivo.…”

Section: Introductionmentioning

confidence: 99%

Stressed out: the skeletal muscle ryanodine receptor as a target of stress

Bellinger¹,

Mongillo²,

Marks³

2008

J. Clin. Invest.

123

120

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Over the past century, understanding the mechanisms underlying muscle fatigue and weakness has been the focus of much investigation. However, the dominant theory in the field, that lactic acidosis causes muscle fatigue, is unlikely to tell the whole story. Recently, dysregulation of sarcoplasmic reticulum (SR) Ca 2+ release has been associated with impaired muscle function induced by a wide range of stressors, from dystrophy to heart failure to muscle fatigue. Here, we address current understandings of the altered regulation of SR Ca 2+ release during chronic stress, focusing on the role of the SR Ca 2+ release channel known as the type 1 ryanodine receptor. IntroductionSkeletal muscle contraction is initiated by depolarization of the surface membrane (the sarcolemma) of muscle cells. Depolarization of the sarcolemma leads to the formation of cross-bridges between myosin and actin and shortening of the basic contractile unit of muscle, the sarcomere, a process known as excitation-contraction (E-C) coupling. Ca 2+ released from intracellular stores is the second messenger that links membrane depolarization to muscle contraction during E-C coupling. Sarcolemmal depolarization propagates down the transverse tubules (T-tubules), which are deep invaginations of the sarcolemma, and activates voltage-gated Cav1.1 Ca 2+ channels (also known as L-type Ca 2+ channels) on the T-tubules. Voltage-induced conformational changes in Cav1.1 activate closely apposed Ca 2+ release channels known as type 1 ryanodine receptors (RyR1s) on the terminal cisternae of the sarcoplasmic reticulum (SR) (1). Ca 2+ release from the SR through RyR1 channels results in a large and rapid rise in the amount of cytoplasmic Ca 2+ , which binds to troponin C and allows myosin and actin to form cross-bridges leading to the sliding of actin and myosin filaments with respect to each other and the shortening of the sarcomere. The result is muscle contraction and generation of force (2-5). The elucidation of the sequence of events during E-C coupling was one of the great advances in physiology in the twentieth century (6).In conditions of prolonged muscular stress (e.g., during the running of a marathon) or in a disease such as heart failure, both of which are characterized by chronic activation of the sympathetic nervous system (SNS), skeletal muscle function is impaired, possibly due to altered E-C coupling. In particular, the amount of Ca 2+ released from the SR during each contraction of the muscle is reduced, aberrant Ca 2+ release events can occur, and Ca 2+ reuptake is slowed (7-9). These observations suggest that the deleterious effects of chronic activation of the SNS on skeletal muscle might be due, at least in part, to defects in Ca 2+ signaling.SR Ca 2+ release channels form an enormous macromolecular signaling complex comprising four approximately 565-kDa RyR1 monomers and several enzymes that are targeted to the cytoplasmic domain of the RyR1 channel, including calstabin1 (also known as FKBP12), cAMP-dependent protein kinase (PKA), protein ...

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Metabolic end products inhibit sarcoplasmic reticulum Ca2+ release and [3H]ryanodine binding

Cited by 108 publications

References 22 publications

Muscle metabolites and performance during high-intensity, intermittent exercise

Muscle metabolites and performance during high-intensity, intermittent exercise

Variation and homogeneity in affective responses to physical activity of varying intensities: An alternative perspective on dose – response based on evolutionary considerations

Stressed out: the skeletal muscle ryanodine receptor as a target of stress

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