Editorial Views  |   January 2018
A Primer for Diagnosing and Managing Malignant Hyperthermia Susceptibility
Author Notes
  • From the North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States, University of Pittsburgh Medical Center, Mercy Hospital, Pittsburgh, Pennsylvania.
  • Corresponding articles on pages 159 and 168.
    Corresponding articles on pages 159 and 168.×
  • Accepted for publication August 8, 2017.
    Accepted for publication August 8, 2017.×
  • Address correspondence to Dr. Larach: mlarach@gmail.com
Article Information
Editorial Views / Patient Safety
Editorial Views   |   January 2018
A Primer for Diagnosing and Managing Malignant Hyperthermia Susceptibility
Anesthesiology 1 2018, Vol.128, 8-10. doi:10.1097/ALN.0000000000001879
Anesthesiology 1 2018, Vol.128, 8-10. doi:10.1097/ALN.0000000000001879
IN this issue, Anesthesiology publishes two comprehensive articles on malignant hyperthermia (MH) susceptibility.1,2  Both highlight the relationship between an anesthetic-induced MH event due to dysregulated skeletal muscle Ca2+ homeostasis and an individual’s susceptibility to that event. Scientists currently believe that MH susceptibility arises from underlying abnormalities in the RYR1 (ryanodine receptor 1 on chromosome 19), the CACNA1S (calcium voltage-gated channel subunit α1 subunit S receptor on chromosome 1), and/or the STAC3 (SH3 and cysteine rich domain 3 protein on chromosome 12) genes.
How are abnormalities in three different chromosomes linked to MH susceptibility? Current research suggests that the RYR1 variants associated with MH susceptibility are missense changes that alter the ryanodine receptor with gain-of-function mutations. These mutations increase calcium release from the skeletal muscle sarcoplasmic reticulum into the cytoplasm. CACNA1S variants suppress the calcium voltage-gated channel’s regulatory effect on RYR1, similarly causing increased calcium flux through the receptor. STAC3 “chaperone” proteins are required to correctly locate the calcium voltage-gated receptor within the skeletal muscle channel.3  Mutated STAC3 receptors increase the amount of calcium released in response to caffeine (an RYR1 agonist) and increase the amount of calcium stored within the sarcoplasmic reticulum.4  Figure 1 in Litman et al.1  depicts the interaction among these receptors and proteins in the skeletal muscle excitation-contraction coupling complex.
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