Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse
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1. We used intact single fibres from a mouse foot muscle to study the role of oxidation-reduction in the modulation of contractile function. 2. The oxidant hydrogen peroxide (H2O2, 100-300 microM) for brief periods did not change myoplasmic Ca2+ concentrations ([Ca2+]i) during submaximal tetani. However, force increased by 27 % during the same contractions. 3. The effects of H2O2 were time dependent. Prolonged exposures resulted in increased resting and tetanic [Ca2+]i, while force was significantly diminished. The force decline was mainly due to reduced myofibrillar Ca2+ sensitivity. There was also evidence of altered sarcoplasmic reticulum (SR) function: passive Ca2+ leak was increased and Ca2+ uptake was decreased. 4. The reductant dithiothreitol (DTT, 0.5-1 mM) did not change tetanic [Ca2+]i, but decreased force by over 40 %. This was completely reversed by subsequent incubations with H2O2. The force decline induced by prolonged exposure to H2O2 was reversed by subsequent exposure to DTT. 5. These results show that the elements of the contractile machinery are differentially responsive to changes in the oxidation-reduction balance of the muscle fibres. Myofibrillar Ca2+ sensitivity appears to be especially susceptible, while the SR functions (Ca2+ leak and uptake) are less so.
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NaNO2 administration can increase cytosolic [Ca2+] without altering force production at a supraphysiological PO2, or lower cytosolic [Ca2+] concomitant with lower submaximal, but not maximal, force at a physiological PO2, during single evoked isometric contractions in isolated mouse muscle fibers.
“There is also previous evidence indicating that NaNO2 administration can increase cytosolic [Ca2+] without altering force production at a supraphysiological PO2 [134], or lower cytosolic [Ca2+] concomitant with lower submaximal, but not maximal, force at a physiological PO2 [118], during single evoked isometric contractions in isolated mouse muscle fibers.”
From Effects of Dietary Nitrate Supplementation on Weightlifting Exercise Performance in Healthy Adults: A Systematic Review (2020) · cites this paper as [134]
The potential candidate mechanisms for improved weightlifting exercise performance after NO3− supplementation include enhanced excitation-contraction coupling via modulation of Ca2+-handling and contractile proteins; improved skeletal muscle metabolic control via lowering the high-energy phosphate cost of contraction and fatigue-related metabolite accumulation; and improved skeletal muscle PerfUSI
“The potential candidate mechanisms for improved weightlifting exercise performance after NO3− supplementation include enhanced excitation–contraction coupling, via modulation of Ca2+-handling and contractile proteins [98,134,135,139]; improved skeletal muscle metabolic control, via lowering the high-energy phosphate cost of contraction and fatigue-related metabolite accumulation [51,94]; and”
From Effects of Dietary Nitrate Supplementation on Weightlifting Exercise Performance in Healthy Adults: A Systematic Review (2020) · cites this paper as [134]
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Self-citation
- Authors
- Andrade, F. H., Reid, M. B., Allen, D. G., & Westerblad, H.
- Affiliations
- University of Kentucky (US)
- Baylor College of Medicine (US)
- The University of Sydney (AU)
- Karolinska Institutet (SE)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 1998-06
- Volume
- 509
- Issue
- 2
- Pages
- 565-575
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2230964
- OpenAlex
- W2074939086
- Cited by
- 438
- References
- 39
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 17 · 2022: 15 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 22 · 2017: 19 · 2016: 21 · 2015: 28 · 2014: 16 · 2013: 24 · 2012: 24
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Karolinska Institutet
- Vetenskapsrådet
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL45721, R01HL045721)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- hydrogen peroxide, dithiothreitol, oxidative stress, redox homeostasis, skeletal muscle contraction, myoplasmic calcium, myofibrillar calcium sensitivity, sarcoplasmic reticulum, calcium leak, calcium uptake, muscle force, tetanic contraction
- MeSH terms
- Animals, Calcium, Dithiothreitol, Hydrogen Peroxide, Male, Mice, Inbred Strains, Muscle Contraction, Myofibrils, Reaction Time, Sarcoplasmic Reticulum, Muscle, Skeletal, Muscle Fibers, Skeletal, Mice, In Vitro Techniques
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