Malignant hyperthermia ≈ Malignant hyperthermia
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Deficiency of TRPM2 leads to embryonic neurogenesis defects in hyperthermia Open
In short, this study reveals the complicated interplay between TRPM2 and β-Cat/SP5 signaling during heat stress.
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Malignant Hyperthermia in the Post-Genomics Era Open
This article reviews advancements in the genetics of malignant hyperthermia, new technologies and approaches for its diagnosis, and the existing limitations of genetic testing for malignant hyperthermia. It also reviews the various RYR1 -r…
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Malignant hyperthermia 2020 Open
Summary Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life‐threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis,…
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Pyrexia: aetiology in the ICU Open
Elevation in core body temperature is one of the most frequently detected abnormal signs in patients admitted to adult ICUs, and is associated with increased mortality in select populations of critically ill patients. The definition of an …
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Clinical Pharmacogenetics Implementation Consortium ( <span>CPIC</span> ) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of <i> <span>RYR</span> 1 </i> or <i> <span>CACNA</span> 1S </i> Genotypes Open
The identification in a patient of 1 of the 50 variants in the RYR 1 or CACNA 1S genes reviewed here should lead to a presumption of malignant hyperthermia susceptibility (MHS). MHS can lead to life‐threatening reactions to potent volatile…
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Review of RyR1 pathway and associated pathomechanisms Open
Ryanodine receptor isoform-1 (RyR1) is a major calcium channel in skeletal muscle important for excitation-contraction coupling. Mutations in the RYR1 gene yield RyR1 protein dysfunction that manifests clinically as RYR1-related congenital…
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Critical Role of Intracellular RyR1 Calcium Release Channels in Skeletal Muscle Function and Disease Open
The skeletal muscle Ca(2+) release channel, also known as ryanodine receptor type 1 (RyR1), is the largest ion channel protein known and is crucial for effective skeletal muscle contractile activation. RyR1 function is controlled by Cav1.1…
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A chemical chaperone improves muscle function in mice with a RyR1 mutation Open
Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca 2+ release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show tha…
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<i>STAC3</i>variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility Open
SH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 …
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Skeletal muscle CaV1.1 channelopathies Open
Ca V 1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its functions as L-type calcium channel. Consequently, all known Ca V 1.1-r…
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TRPV1 variants impair intracellular Ca2+ signaling and may confer susceptibility to malignant hyperthermia Open
We propose that TRPV1 contributes to MH and could represent an actionable therapeutic target for prevention of the pathology and also be responsible for MH sensitivity when mutated.
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Succinylcholine Use and Dantrolene Availability for Malignant Hyperthermia Treatment Open
EDITOR’S PERSPECTIVE What We Already Know about This Topic Dantrolene effectively treats malignant hyperthermia, but there are discrepant recommendations for dantrolene availability in facilities that stock succinylcholine for airway rescu…
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Dantrolene requires Mg <sup>2+</sup> to arrest malignant hyperthermia Open
Significance The nature of overactive Ca 2+ release in malignant hyperthermia (MH) and the mechanism of action of the drug dantrolene that arrests MH events are poorly understood. Here, we show that dantrolene stops overactive Ca 2+ releas…
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An Assessment of Penetrance and Clinical Expression of Malignant Hyperthermia in Individuals Carrying Diagnostic Ryanodine Receptor 1 Gene Mutations Open
Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Malignant hyperthermia (MH) is a potentially lethal disorder triggered by certain anesthetics. Mutations in the ryanodine receptor…
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Congenital myopathy results from misregulation of a muscle Ca <sup>2+</sup> channel by mutant Stac3 Open
Significance Skeletal muscle contractions are regulated by a process called excitation–contraction (EC) coupling, and defects in it are associated with numerous human myopathies. Recently, stac3 (SH3 and cysteine-rich domain 3) was identif…
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A novel RyR1-selective inhibitor prevents and rescues sudden death in mouse models of malignant hyperthermia and heat stroke Open
Mutations in the type 1 ryanodine receptor (RyR1), a Ca 2+ release channel in skeletal muscle, hyperactivate the channel to cause malignant hyperthermia (MH) and are implicated in severe heat stroke. Dantrolene, the only approved drug for …
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Congenital myopathies: not only a paediatric topic Open
Purpose of review This article reviews adult presentations of the major congenital myopathies – central core disease, multiminicore disease, centronuclear myopathy and nemaline myopathy – with an emphasis on common genetic backgrounds, typ…
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Updated variant curation expert panel criteria and pathogenicity classifications for 251 variants for <i>RYR1</i> -related malignant hyperthermia susceptibility Open
The ClinGen malignant hyperthermia susceptibility (MHS) variant curation expert panel specified the American College of Medical Genetics and Genomics/Association of Molecular Pathologists (ACMG/AMP) criteria for RYR1-related MHS and a pilo…
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An <i>RYR1</i> mutation associated with malignant hyperthermia is also associated with bleeding abnormalities Open
Gain-of-function RYR1 mutations cause increased Ca 2+ sparks in vascular smooth muscle cells and prolong bleeding.
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Heat-Induced Calcium Leakage Causes Mitochondrial Damage in<i>Caenorhabditis elegans</i>Body-Wall Muscles Open
Acute onset of organ failure in heatstroke is triggered by rhabdomyolysis of skeletal muscle. Here, we showed that elevated temperature increases free cytosolic Ca2+ [Ca2+]f from RYR (ryanodine receptor)/UNC-68 in vivo in the muscles of an…
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The current status of malignant hyperthermia Open
Malignant hyperthermia (MH) is a rare and life-threatening pharmacogenetic disorder triggered by volatile anesthetics, the depolarizing muscle relaxant succinylcholine, and rarely by strenuous exercise or environmental heat. The exact prev…
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Junctional membrane Ca <sup>2+</sup> dynamics in human muscle fibers are altered by malignant hyperthermia causative RyR mutation Open
Significance In human muscle with ryanodine receptor (RyR) variants, there is expected to be a change in the basal RyRs Ca 2+ leak that may alter local Ca 2+ dynamics. It is not currently possible to assess these basal Ca 2+ dynamics in hu…
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Ryanodine receptor leak triggers fiber Ca <sup>2+</sup> redistribution to preserve force and elevate basal metabolism in skeletal muscle Open
RyR1 Ca 2+ leak causes a cascade of events that shifts Ca 2+ to the cytoplasm and mitochondria, supporting force generation.
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Dantrolene : From Malignant Hyperthermia to Alzheimer’s Disease Open
Dantrolene, a ryanodine receptor antagonist, is primarily known as the only clinically acceptable and effective treatment for Malignant Hyperthermia (MH). Inhibition of Ryanodine Receptor (RyR) by dantrolene decreases the abnormal calcium …
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RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction Open
Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide spectrum of inherited myopathies presenting throughout life. Malignant hyperthermia susceptibility (MHS)-related RYR1 mutations have emerged as a co…
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Genomic Screening for Malignant Hyperthermia Susceptibility Open
It is timely to consider the utility and practicability of screening for malignant hyperthermia susceptibility using genomic testing. Here the authors pose a simple, but bold question: what would it take to end deaths from malignant hypert…
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Strenuous exercise triggers a life‐threatening response in mice susceptible to malignant hyperthermia Open
In humans, hyperthermic episodes can be triggered by halogenated anesthetics [malignant hyperthermia (MH) susceptibility] and by high temperature [environmental heat stroke (HS)]. Correlation between MH susceptibility and HS is supported b…
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Functional Calsequestrin-1 Is Expressed in the Heart and Its Deficiency Is Causally Related to Malignant Hyperthermia-Like Arrhythmia Open
Background: Calsequestrins (Casqs), comprising the Casq1 and Casq2 isoforms, buffer Ca 2+ and regulate its release in the sarcoplasmic reticulum of skeletal and cardiac muscle, respectively. Human inherited diseases associated with mutatio…
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Comparison of Chlorantraniliprole and Flubendiamide Activity Toward Wild-Type and Malignant Hyperthermia-Susceptible Ryanodine Receptors and Heat Stress Intolerance Open
Chlorantraniliprole (CP) and flubendiamide (FD) are widely used in agriculture globally to control lepidopteran pests. Both insecticides target ryanodine receptors (RyRs) and promote Ca2+ leak from sarcoplasmic reticulum (SR) within insect…
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Reduced threshold for store overload-induced Ca2+ release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease Open
Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), whereas mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachy…