ArticleAmerican journal of physiology. Cell physiology2008
Halothane modulation of skeletal muscle ryanodine receptors: dependence on Ca2+, Mg2+, and ATP.
Article in American journal of physiology. Cell physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Distinct pathophysiological characteristics in developing muscle from patients susceptible to malignant hyperthermia.British journal of anaesthesia · 2023Article
- Molecular Aspects Implicated in Dantrolene Selectivity with Respect to Ryanodine Receptor Isoforms.International journal of molecular sciences · 2023Article
- Organelle membrane derived patches: reshaping classical methods for new targets.Scientific reports · 2017Article
- Strenuous exercise triggers a life-threatening response in mice susceptible to malignant hyperthermia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Dantrolene requires MgProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mind the magnesium, in dantrolene suppression of malignant hyperthermia.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- PharmGKB summary: very important pharmacogene information for RYR1.Pharmacogenetics and genomics · 2016Review
- Oxidation of ryanodine receptor (RyR) and calmodulin enhance Ca release and pathologically alter, RyR structure and calmodulin affinity.Journal of molecular and cellular cardiology · 2015Article
- Essential Role of Calmodulin in RyR Inhibition by Dantrolene.Molecular pharmacology · 2015Article
- The couplonopathies: A comparative approach to a class of diseases of skeletal and cardiac muscle.The Journal of general physiology · 2015Review
- The effect of succinylcholine on malignant hyperthermia events in susceptible swine.BMC anesthesiology · 2014Article
- Drosophila ryanodine receptors mediate general anesthesia by halothane.Anesthesiology · 2013Article
- Coupled gating of skeletal muscle ryanodine receptors is modulated by Ca2+, Mg2+, and ATP.American journal of physiology. Cell physiology · 2012Article
- Dantrolene prevents arrhythmogenic Ca2+ release in heart failure.American journal of physiology. Heart and circulatory physiology · 2012Article
- CGP-37157 inhibits the sarcoplasmic reticulum Ca²+ ATPase and activates ryanodine receptor channels in striated muscle.Molecular pharmacology · 2011Article
- The cytoprotective effects of dantrolene: a ryanodine receptor antagonist.Anesthesia and analgesia · 2010Review
- Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Malignant hyperthermia (MH) susceptibility is a genetic disorder of skeletal muscle associated with mutations in the ryanodine receptor isoform 1 (RyR1) of sarcoplasmic reticulum (SR). In MH-susceptible skeletal fibers, RyR1-mediated Ca(2+) release is highly sensitive to activation by the volatile anesthetic halothane. Indeed, studies with isolated RyR1 channels (using simple Cs(+) solutions) found that halothane selectively affects mutated but not wild-type RyR1 function. However, studies in skeletal fibers indicate that halothane can also activate wild-type RyR1-mediated Ca(2+) release. We hypothesized that endogenous RyR1 agonists (ATP, lumenal Ca(2+)) may increase RyR1 sensitivity to halothane. Consequently, we studied how these agonists affect halothane action on rabbit skeletal RyR1 reconstituted into planar lipid bilayers. We found that cytosolic ATP is required for halothane-induced activation of the skeletal RyR1. Unlike RyR1, cardiac RyR2 (much less sensitive to ATP) responded to halothane even in the absence of this agonist. ATP-dependent halothane activation of RyR1 was enhanced by cytosolic Ca(2+) (channel agonist) and counteracted by Mg(2+) (channel inhibitor). Dantrolene, a muscle relaxant used to treat MH episodes, did not affect RyR1 or RyR2 basal activity and did not interfere with halothane-induced activation. Studies with skeletal SR microsomes confirmed that halothane-induced RyR1-mediated SR Ca(2+) release is enhanced by high ATP-low Mg(2+) in the cytosol and by increased SR Ca(2+) load. Thus, physiological or pathological processes that induce changes in cellular levels of these modulators could affect RyR1 sensitivity to halothane in skeletal fibers, including the outcome of halothane-induced contracture tests used to diagnose MH susceptibility.
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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.