Neuromuscular Disorders and Malignant Hyperthermia

Zhou, Jerry; Allen, Paul D.; Pessah, Isaac N.; Naguib, Mohamed

doi:10.1016/b978-0-443-06959-8.00037-6

Cited by 28 publications

(31 citation statements)

References 234 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…M alignant hyperthermia (MH) is a potentially fatal, pharmacogenetic disorder that can be triggered by depolarizing muscle relaxants or halogenated anesthetics (1). Following exposure to one of these triggers, MH-susceptible individuals enter a hypermetabolic crisis characterized by tachycardia, muscle rigidity, rhabdomyolysis, increased oxidative/nitrosative stress, mitochondrial damage, acidosis, hypercapnia, and renal failure leading ultimately to death.…”

Section: 4-dihydropyridine Receptor | α Ismentioning

confidence: 99%

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor

Eltit

Bannister²,

Moua

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Malignant hyperthermia (MH) susceptibility is a dominantly inherited disorder in which volatile anesthetics trigger aberrant Ca 2+ release in skeletal muscle and a potentially fatal rise in perioperative body temperature. Mutations causing MH susceptibility have been identified in two proteins critical for excitation-contraction (EC) coupling, the type 1 ryanodine receptor (RyR1) and Ca V 1.1, the principal subunit of the L-type Ca 2+ channel. All of the mutations that have been characterized previously augment EC coupling and/or increase the rate of L-type Ca 2+ entry. The Ca V 1.1 mutation R174W associated with MH susceptibility occurs at the innermost basic residue of the IS4 voltage-sensing helix, a residue conserved among all Ca V channels [Carpenter D, et al. (2009) BMC Med Genet 10:104-115.]. To define the functional consequences of this mutation, we expressed it in dysgenic (Ca V 1.1 null) myotubes. Unlike previously described MH-linked mutations in Ca V 1.1, R174W ablated the L-type current and had no effect on EC coupling. Nonetheless, R174W increased sensitivity of Ca 2+ release to caffeine (used for MH diagnostic in vitro testing) and to volatile anesthetics. Moreover, in Ca V 1.1 R174W-expressing myotubes, resting myoplasmic Ca 2+ levels were elevated, and sarcoplasmic reticulum (SR) stores were partially depleted, compared with myotubes expressing wild-type Ca V 1.1. Our results indicate that Ca V 1.1 functions not only to activate RyR1 during EC coupling, but also to suppress resting RyR1-mediated Ca 2+ leak from the SR, and that perturbation of Ca V 1.1 negative regulation of RyR1 leak identifies a unique mechanism that can sensitize muscle cells to MH triggers.

show abstract

Section: 4-dihydropyridine Receptor | α Ismentioning

confidence: 99%

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor

Eltit

Bannister²,

Moua

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…3 is a pharmacogenetic, life-threatening syndrome triggered in susceptible individuals by volatile general anesthetics, depolarizing neuromuscular blocking agents, and heat stress (2). An MH episode is characterized by increased expired CO 2 , rapid onset of metabolic acidosis, elevated core temperature, and sustained muscle contraction.…”

Section: Fulminant Malignant Hyperthermia (Mh)mentioning

confidence: 99%

Gene Dose Influences Cellular and Calcium Channel Dysregulation in Heterozygous and Homozygous T4826I-RYR1 Malignant Hyperthermia-susceptible Muscle

Barrientos

Feng

Truong

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background:Muscle from heterozygous and homozygous T4826I-RYR1 MH-susceptible mice is investigated for biochemical and cellular abnormalities. Results: T4826I-RYR1 gene dose determines severity of [Ca 2ϩ ] rest , mitochondrial, EC coupling, and Ca 2ϩ channel impairments. Conclusion: T4826I-RYR1 channel dysfunction is regulated in vivo but imparts susceptibility to environmental triggers. Significance: T4826I-RYR1 is sufficient to confer MHS strongly dependent on gene dose.

show abstract

“…Human malignant hyperthermia (MH)-susceptible patients remain subclinical until challenged with one or more pharmacological triggering agents, including halogenated volatile anesthetics and depolarizing neuromuscular blockers (Zhou et al, 2010). A fulminant MH episode during the perioperative period is often lethal if not promptly treated with dantrolene.…”

Section: Introductionmentioning

confidence: 99%

“…When a familial history of MH is suspected (Lehmann-Horn et al, 2008), MH susceptibility (MHS) is typically diagnosed with an in vitro contracture test. Although in vitro contracture test testing is a good prognosticator of MH, fatal cases continue to occur annually in the United States and throughout the world (Zhou et al, 2010). MHS is an inherited autosomal dominant muscle disorder with a heterogeneous etiology.…”

Section: Introductionmentioning

confidence: 99%

Functional and Biochemical Properties of Ryanodine Receptor Type 1 Channels from Heterozygous R163C Malignant Hyperthermia-Susceptible Mice

et al. 2010

Self Cite

View full text Add to dashboard Cite

ABSTRACT3 H]Ry receptor occupancy; 3) comparatively higher channel activity, even in reducing glutathione buffer; 4) enhanced RyR1 activity both at 25 and 37°C; and 5) elevated cytoplasmic [Ca 2ϩ ] rest . R163C channels are inherently more active than WT channels, a functional impairment that cannot be reversed by dephosphorylation with protein phosphatase. Dysregulated R163C channels produce a more overt phenotype in myotubes than in adult fibers in the absence of triggering agents, suggesting tighter negative regulation of R163C-RyR1 within the Ca 2ϩ release unit of adult fibers.

show abstract

Neuromuscular Disorders and Malignant Hyperthermia

Cited by 28 publications

References 234 publications

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor

Gene Dose Influences Cellular and Calcium Channel Dysregulation in Heterozygous and Homozygous T4826I-RYR1 Malignant Hyperthermia-susceptible Muscle

Functional and Biochemical Properties of Ryanodine Receptor Type 1 Channels from Heterozygous R163C Malignant Hyperthermia-Susceptible Mice

Contact Info

Product

Resources

About

Neuromuscular Disorders and Malignant Hyperthermia

Cited by 28 publications

References 234 publications

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca 2+ channel and the type 1 ryanodine receptor

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca 2+ channel and the type 1 ryanodine receptor

Gene Dose Influences Cellular and Calcium Channel Dysregulation in Heterozygous and Homozygous T4826I-RYR1 Malignant Hyperthermia-susceptible Muscle

Functional and Biochemical Properties of Ryanodine Receptor Type 1 Channels from Heterozygous R163C Malignant Hyperthermia-Susceptible Mice

Contact Info

Product

Resources

About

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor