Effects of Calcium-free Solution, Calcium Antagonists, and the Calcium Agonist BAY K 8644 on Mechanical Responses of Skeletal Muscle from Patients Susceptible to Malignant Hyperthermia

Adnet, P.; Krivosic-Horber, R; Adamantidis, M. M.; Reyford, H.; Cordonnier, Corinne; Haudecoeur, G.

doi:10.1097/00000542-199109000-00006

Cited by 18 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In-vitro contracture tests used to diagnose MHS only work when extracellular Ca 2+ is included in the solution bathing the muscle biopsy, 46–48 suggesting that Ca 2+ influx may play a critical role in the MH crises. Interestingly, store-operated Ca 2+ entry (SOCE), a Ca 2+ influx mechanism triggered by store depletion in which STIM1 Ca 2+ sensors in the SR activate Ca 2+ influx through Orai1 Ca 2+ channels in the transverse tubule membrane, 49,50 is significantly enhanced in human skeletal fibers from MHS patients.…”

Section: Discussionmentioning

confidence: 99%

Antioxidants Protect Calsequestrin-1 Knockout Mice from Halothane- and Heat-induced Sudden Death

et al. 2015

View full text Add to dashboard Cite

Background Mice lacking calsequestrin-1 (CASQ1-null), a Ca2+ binding protein that modulates the activity of Ca2+ release in skeletal muscle, exhibit lethal hypermetabolic episodes that resemble malignant hyperthermia (MH) in humans when exposed to halothane or heat stress. Methods As oxidative species may play a critical role in MH crises, we treated CASQ1-null mice with two antioxidants, N-acetylcysteine (NAC provided ad libitum in drinking water) and Trolox (administered by intra-peritoneal injection), before exposure to halothane (2%, 1 h) or heat (41°C, 1 h). Results NAC and Trolox significantly protected CASQ1-null mice from lethal episodes, with mortality being: 79% (n=14), 25% (n=16) and 20% (n=5) during halothane exposure and 86% (n=21), 29% (n=21) and 33% (n=6) during heat-stress in un-treated, NAC- and Trolox- treated mice, respectively. During heat challenge, the increase in core temperature in CASQ1-null mice (42.3±0.1°C, n=10) was significantly reduced by both NAC and Trolox (40.6±0.3°C, n=6; 40.5±0.2°C, n=6). NAC treatment of CASQ1-null muscles/mice normalized caffeine sensitivity during in-vitro contracture tests, Ca2+ transients in single fibers, and significantly reduced the percentage of fibers undergoing rhabdomyolysis (37.6±2.5%, 38/101 fibers in 3 mice; 11.6±1.1%, 21/186 fibers in 5 mice respectively). The protective effect of antioxidant treatment likely resulted from mitigation of oxidative stress, as NAC reduced mitochondrial superoxide production, superoxide dismutase type-1 (SOD1) and 3-nitrotyrosine (3-NT) expression, and increased both reduced glutathione (GSH) and GSH/GSSG ratio. Conclusions These studies provide a deeper understanding of the mechanisms that underlie hyperthermic crises in calsequestrin-1 deficient muscle and demonstrate that antioxidant pre-treatment may prevent them.

show abstract

Section: Discussionmentioning

confidence: 99%

Antioxidants Protect Calsequestrin-1 Knockout Mice from Halothane- and Heat-induced Sudden Death

et al. 2015

View full text Add to dashboard Cite

show abstract

“…5 The sensitivity of this latter method may be inadequate as the technique itself excludes any detection of a possible defect in the sarcolemma. 4 Differences were also observed in the criteria used for diagnosing malignant hyperthermia based on in vitro contracture tests: 13 some centres used the development of a contracture of >0.5 g force in response to 1% halothane as a threshold while others chose >0.7 g force in response to 3% halothane. The European malignant hyperthermia group 17 required, for an abnormal response to halothane, a contracture of >0.2 g force in response to <2% halothane.…”

Section: Primary Skeletal Muscle Defect Similar To Malignant Hyperthementioning

confidence: 99%

Neuroleptic malignant syndrome

Adnet

Lestavel

Krivosic-Horber

2000

British Journal of Anaesthesia

258

242

View full text Add to dashboard Cite

“…Indeed, early studies conducted during the development of the in vitro caffeine and halothane contracture test, the gold standard for MH diagnosis in North America, revealed that this test fails when conducted using Ca 2+ -free extracellular solutions [16-19]. More recently, increased SOCE activation during halothane-induced Ca 2+ release was demonstrated in mechanically skinned human skeletal muscle fibers from MH susceptible patients [20].…”

Section: Introductionmentioning

confidence: 99%

Accelerated Activation of SOCE Current in Myotubes from Two Mouse Models of Anesthetic- and Heat-Induced Sudden Death

2013

View full text Add to dashboard Cite

Store-operated calcium entry (SOCE) channels play an important role in Ca2+ signaling. Recently, excessive SOCE was proposed to play a central role in the pathogenesis of malignant hyperthermia (MH), a pharmacogenic disorder of skeletal muscle. We tested this hypothesis by characterizing SOCE current (ISkCRAC) magnitude, voltage dependence, and rate of activation in myotubes derived from two mouse models of anesthetic- and heat-induced sudden death: 1) type 1 ryanodine receptor (RyR1) knock-in mice (Y524S/+) and 2) calsequestrin 1 and 2 double knock-out (dCasq-null) mice. ISkCRAC voltage dependence and magnitude at -80 mV were not significantly different in myotubes derived from wild type (WT), Y524S/+ and dCasq-null mice. However, the rate of ISkCRAC activation upon repetitive depolarization was significantly faster at room temperature in myotubes from Y524S/+ and dCasq-null mice. In addition, the maximum rate of ISkCRAC activation in dCasq-null myotubes was also faster than WT at more physiological temperatures (35-37°C). Azumolene (50 µM), a more water-soluble analog of dantrolene that is used to reverse MH crises, failed to alter ISkCRAC density or rate of activation. Together, these results indicate that while an increased rate of ISkCRAC activation is a common characteristic of myotubes derived from Y524S/+ and dCasq-null mice and that the protective effects of azumolene are not due to a direct inhibition of SOCE channels.

show abstract

Effects of Calcium-free Solution, Calcium Antagonists, and the Calcium Agonist BAY K 8644 on Mechanical Responses of Skeletal Muscle from Patients Susceptible to Malignant Hyperthermia

Cited by 18 publications

References 0 publications

Antioxidants Protect Calsequestrin-1 Knockout Mice from Halothane- and Heat-induced Sudden Death

Antioxidants Protect Calsequestrin-1 Knockout Mice from Halothane- and Heat-induced Sudden Death

Neuroleptic malignant syndrome

Accelerated Activation of SOCE Current in Myotubes from Two Mouse Models of Anesthetic- and Heat-Induced Sudden Death

Contact Info

Product

Resources

About