ArticleBiophysical journal1997
Reduced inhibitory effect of Mg2+ on ryanodine receptor-Ca2+ release channels in malignant hyperthermia.
Article in Biophysical journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 102 citations in OpenAlex.
- Structural and Functional Regulation of RyR2 in Cardiac Calcium Handling and Arrhythmogenesis.Biomedicines · 2026Review
- Magnesium Administration in Preslaughter Drinking Water Reduces Spinal Fractures in Pigs during Stunning.ACS omega · 2026Article
- Review
- Modeling the mechanism of Ca2+ release in skeletal muscle by DHPRs easing inhibition at RyR I1-sites.The Journal of general physiology · 2024Article
- Interplay between MgNature communications · 2024Article
- Molecular Aspects Implicated in Dantrolene Selectivity with Respect to Ryanodine Receptor Isoforms.International journal of molecular sciences · 2023Article
- 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
- Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse.Journal of cell science · 2019Article
- Regulation of the RyR channel gating by CaBiophysical reviews · 2018Review
- Mind the magnesium, in dantrolene suppression of malignant hyperthermia.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Dantrolene requires MgProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Extensive Ca2+ leak through K4750Q cardiac ryanodine receptors caused by cytosolic and luminal Ca2+ hypersensitivity.The Journal of general physiology · 2017Article
- Activation and propagation of Ca2+ release from inside the sarcoplasmic reticulum network of mammalian skeletal muscle.The Journal of physiology · 2014Article
- Differences in the regulation of RyR2 from human, sheep, and rat by Ca²⁺ and Mg²⁺ in the cytoplasm and in the lumen of the sarcoplasmic reticulum.The Journal of general physiology · 2014Article
- Ryanodine receptors: physiological function and deregulation in Alzheimer disease.Molecular neurodegeneration · 2014Review
- Nonspecific sarcolemmal cation channels are critical for the pathogenesis of malignant hyperthermia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Phospholamban phosphorylation increases the passive calcium leak from cardiac sarcoplasmic reticulum.Pflugers Archiv : European journal of physiology · 2012Article
- Intercellular Ca(2+) waves: mechanisms and function.Physiological reviews · 2012Review
- Synthetic localized calcium transients directly probe signalling mechanisms in skeletal muscle.The Journal of physiology · 2012Article
- Gene dose influences cellular and calcium channel dysregulation in heterozygous and homozygous T4826I-RYR1 malignant hyperthermia-susceptible muscle.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant hyperthermia (MH) is a potentially fatal, inherited skeletal muscle disorder in humans and pigs that is caused by abnormal regulation of Ca2+ release from the sarcoplasmic reticulum (SR). MH in pigs is associated with a single mutation (Arg615Cys) in the SR ryanodine receptor (RyR) Ca2+ release channel. The way in which this mutation leads to excessive Ca2+ release is not known and is examined here. Single RyR channels from normal and MH-susceptible (MHS) pigs were examined in artificial lipid bilayers. High cytoplasmic (cis) concentrations of either Ca2+ or Mg2+ (>100 microM) inhibited channel opening less in MHS RyRs than in normal RyRs. This difference was more prominent at lower ionic strength (100 mM versus 250 mM). In 100 mM cis Cs+, half-maximum inhibition of activity occurred at approximately 100 microM Mg2+ in normal RyRs and at approximately 300 microM Mg2+ in MHS RyRs, with an average Hill coefficient of approximately 2 in both cases. The level of Mg2+ inhibition was not appreciably different in the presence of either 1 or 50 microM activating Ca2+, showing that it was not substantially influenced by competition between Mg2+ and Ca2+ for the Ca2+ activation site. Even though the absolute inhibitory levels varied widely between channels and conditions, the inhibitory effects of Ca2+ and Mg2+ were virtually identical for the same conditions in any given channel, indicating that the two cations act at the same low-affinity inhibitory site. It seems likely that at the cytoplasmic [Mg2+] in vivo (approximately 1 mM), this Ca2+/Mg2+-inhibitory site will be close to fully saturated with Mg2+ in normal RyRs, but less fully saturated in MHS RyRs. Therefore MHS RyRs should be more sensitive to any activating stimulus, which would readily account for the development of an MH episode.
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