Understanding malignant hyperthermia: each move forward opens our eyes to the distance left to travel.

@article{Dirksen2019UnderstandingMH,
  title={Understanding malignant hyperthermia: each move forward opens our eyes to the distance left to travel.},
  author={Robert T. Dirksen and Paul D. Allen and J. R. L{\'o}pez},
  journal={British journal of anaesthesia},
  year={2019},
  volume={122 1},
  pages={
          8-9
        }
}

References

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Pharmacologic and Functional Characterization of Malignant Hyperthermia in the R163C RyR1 Knock-in Mouse
TLDR
Heterozygous R163C mice represent a valid model for studying the mechanisms that cause the human malignant hyperthermia syndrome and a diminished inhibitory regulation by Mg2+.
Voltage modulates halothane-triggered Ca2+ release in malignant hyperthermia-susceptible muscle
TLDR
It is concluded that the binding of halothane to RyR1 alters the voltage dependence of Ca2+ release in MH-susceptible muscle fibers such that the resting membrane potential becomes a decisive factor for the efficiency of the drug to trigger Ca2- release.
Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study
TLDR
An MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release.
Effects of dantrolene on myoplasmic free [Ca2+] measured in vivo in patients susceptible to malignant hyperthermia.
TLDR
The results of the study extend the previous findings in humans and swine and demonstrate that it is possible to measure myoplasmic free [Ca2+] in vivo in humans.
Distinct effects on Ca2+ handling caused by malignant hyperthermia and central core disease mutations in RyR1.
TLDR
It is concluded that MH-only mutations modestly increase basal release-channel activity in a manner insufficient to alter net SR Ca2+ content ("compensated leak"), whereas the mixed MH + CCD phenotype arises from mutations that enhance basal activity to a level sufficient to promote SR Ca 2+ depletion, elevate [Ca2+]i, and reduce maximal VGCR.
Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population
TLDR
Novel mutations described in this study will contribute to the worldwide pool of MH-associated mutations in the RYR1 gene, ultimately increasing the value of MH genetic diagnostic testing.
Mice expressing T4826I‐RYR1 are viable but exhibit sex‐ and genotype‐dependent susceptibility to malignant hyperthermia and muscle damage
TLDR
These data demonstrate that an MHS mutation within the S4‐S5∗∗ ∗∷∗ cytoplasmic linker of RYR1 confers genotype‐ and sex‐dependent susceptibility to pharmacological and environmental stressors that trigger fulminant MH and promote myopathy.
Measurement of Resting Cytosolic Ca2+ Concentrations and Ca2+ Store Size in HEK-293 Cells Transfected with Malignant Hyperthermia or Central Core Disease Mutant Ca2+ Release Channels*
TLDR
The content of endogenous sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2b (SERCA2b), measured by enzyme-linked immunosorbent assay,45Ca2+ uptake, and confocal microscopy, was increased in HEK-293 cells expressing wild type or mutant RyR1, supporting the view that endoplasmic retention capacity is increased as a compensatory response to an enhanced Ca 2+ leak.
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