ArticleThe Journal of biological chemistry2011
Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- OXPHOS complex deficiency in congenital myopathy: A systematic review.European journal of clinical investigation · 2025Pooled it
- Mitochondrial bioenergetics and intracellular calcium concentration in primary myotubes from mouse models of malignant hyperthermia.British journal of anaesthesia · 2026Article
- Article
- An Association between OXPHOS-Related Gene Expression and Malignant Hyperthermia Susceptibility in Human Skeletal Muscle Biopsies.International journal of molecular sciences · 2024Article
- Calcium-Dependent Interaction of Nitric Oxide Synthase with CytochromeBrain sciences · 2023Article
- Targeting activin receptor-like kinase 7 ameliorates adiposity and associated metabolic disorders.JCI insight · 2023Article
- Unravelling the unseen metabolic changes in patients with malignant hyperthermia.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2021Article
- Untargeted metabolomics profiling of skeletal muscle samples from malignant hyperthermia susceptible patients.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2021Article
- Article
- T lymphocytes from malignant hyperthermia-susceptible mice display aberrations in intracellular calcium signaling and mitochondrial function.Cell calcium · 2021Article
- Bioenergetic defects in muscle fibers ofThe Journal of biological chemistry · 2020Article
- Dietary Caffeine Synergizes Adverse Peripheral and Central Responses to Anesthesia in Malignant Hyperthermia Susceptible Mice.Molecular pharmacology · 2020Article
- Sex-specific alterations in whole body energetics and voluntary activity in heterozygous R163C malignant hyperthermia-susceptible mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990-2019.Orphanet journal of rare diseases · 2020Article
- Cored in the act: the use of models to understand core myopathies.Disease models & mechanisms · 2019Review
- Ileal interposition surgery targets the hepatic TGF-β pathway, influencing gluconeogenesis and mitochondrial bioenergetics in the UCD-T2DM rat model of diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Permeabilised skeletal muscle reveals mitochondrial deficiency in malignant hyperthermia-susceptible individuals.British journal of anaesthesia · 2019Article
- Malignant Hyperthermia in the Post-Genomics Era: New Perspectives on an Old Concept.Anesthesiology · 2018Review
- Mitochondrial cardiomyopathies feature increased uptake and diminished efflux of mitochondrial calcium.Journal of molecular and cellular cardiology · 2017Article
- Mitochondrial-nuclear crosstalk, haplotype and copy number variation distinct in muscle fiber type, mitochondrial respiratory and metabolic enzyme activities.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Malignant hyperthermia (MH) and central core disease in humans have been associated with mutations in the skeletal ryanodine receptor (RyR1). Heterozygous mice expressing the human MH/central core disease RyR1 R163C mutation exhibit MH when exposed to halothane or heat stress. Considering that many MH symptoms resemble those that could ensue from a mitochondrial dysfunction (e.g. metabolic acidosis and hyperthermia) and that MH-susceptible mice or humans have a higher than normal cytoplasmic Ca(2+) concentration at rest, we evaluated the role of mitochondria in skeletal muscle from R163C compared with wild type mice under basal (untriggered) conditions. R163C skeletal muscle exhibited a significant increase in matrix Ca(2+), increased reactive oxygen species production, lower expression of mitochondrial proteins, and higher mtDNA copy number. These changes, in conjunction with lower myoglobin and glycogen contents, Myh4 and GAPDH transcript levels, GAPDH activity, and lower glucose utilization suggested a switch to a compromised bioenergetic state characterized by both low oxidative phosphorylation and glycolysis. The shift in bioenergetic state was accompanied by a dysregulation of Ca(2+)-responsive signaling pathways regulated by calcineurin and ERK1/2. Chronically elevated resting Ca(2+) in R163C skeletal muscle elicited the maintenance of a fast-twitch fiber program and the development of insulin resistance-like phenotype as part of a metabolic adaptation to the R163C RyR1 mutation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.