Molecular Basis for Exercise-Induced Fatigue: The Importance of Strictly Controlled Cellular Ca 2+ Handling

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The contractile function of skeletal muscle declines during intense or prolonged physical exercise, that is, fatigue develops. Skeletal muscle fibers fatigue acutely during highly intense exercise when they have to rely on anaerobic metabolism. Early stages of fatigue involve impaired myofibrillar function, whereas decreased Ca 2+ release from the sarcoplasmic reticulum (SR) becomes more important in later stages. SR Ca 2+ release can also become reduced with more prolonged, lower intensity exercise, and it is then related to glycogen depletion. Increased reactive oxygen/nitrogen species can cause long-lasting impairments in SR Ca 2+ release resulting in a prolonged force depression after exercise. In this article, we discuss molecular and cellular mechanisms of the above fatigue-induced changes, with special focus on multiple mechanisms to decrease SR Ca 2+ release to avoid energy depletion and preserve muscle fiber integrity. We also discuss fatigue-related effects of exercise-induced Ca 2+ fluxes over the sarcolemma and between the cytoplasm and mitochondria.

Related collections

Most cited references 124

Record: found
Abstract: found
Article: not found

Antioxidants prevent health-promoting effects of physical exercise in humans.

Michael Ristow, Kim Zarse, Andreas Oberbach … (2009)

Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARgamma), and PPARgamma coactivators PGC1alpha and PGC1beta only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.

0 comments Cited 468 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

NCLX is an essential component of mitochondrial Na+/Ca2+ exchange.

Raz Palty, William Silverman, Michal Hershfinkel … (2010)

Mitochondrial Ca(2+) efflux is linked to numerous cellular activities and pathophysiological processes. Although it is established that an Na(+)-dependent mechanism mediates mitochondrial Ca(2+) efflux, the molecular identity of this transporter has remained elusive. Here we show that the Na(+)/Ca(2+) exchanger NCLX is enriched in mitochondria, where it is localized to the cristae. Employing Ca(2+) and Na(+) fluorescent imaging, we demonstrate that mitochondrial Na(+)-dependent Ca(2+) efflux is enhanced upon overexpression of NCLX, is reduced by silencing of NCLX expression by siRNA, and is fully rescued by the concomitant expression of heterologous NCLX. NCLX-mediated mitochondrial Ca(2+) transport was inhibited, moreover, by CGP-37157 and exhibited Li(+) dependence, both hallmarks of mitochondrial Na(+)-dependent Ca(2+) efflux. Finally, NCLX-mediated mitochondrial Ca(2+) exchange is blocked in cells expressing a catalytically inactive NCLX mutant. Taken together, our results converge to the conclusion that NCLX is the long-sought mitochondrial Na(+)/Ca(2+) exchanger.

0 comments Cited 263 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging.

Alisa Umanskaya, Alain Lacampagne, Wenjun Xie … (2011)

Age-related loss of muscle mass and force (sarcopenia) contributes to disability and increased mortality. Ryanodine receptor 1 (RyR1) is the skeletal muscle sarcoplasmic reticulum calcium release channel required for muscle contraction. RyR1 from aged (24 months) rodents was oxidized, cysteine-nitrosylated, and depleted of the channel-stabilizing subunit calstabin1, compared to RyR1 from younger (3-6 months) adults. This RyR1 channel complex remodeling resulted in "leaky" channels with increased open probability, leading to intracellular calcium leak in skeletal muscle. Similarly, 6-month-old mice harboring leaky RyR1-S2844D mutant channels exhibited skeletal muscle defects comparable to 24-month-old wild-type mice. Treating aged mice with S107 stabilized binding of calstabin1 to RyR1, reduced intracellular calcium leak, decreased reactive oxygen species (ROS), and enhanced tetanic Ca(2+) release, muscle-specific force, and exercise capacity. Taken together, these data indicate that leaky RyR1 contributes to age-related loss of muscle function. Copyright © 2011 Elsevier Inc. All rights reserved.