Putative malignant hyperthermia mutation Ca_V1.1-R174W is insufficient to trigger a fulminant response to halothane or confer heat stress intolerance.

ABSTRACT: Malignant hyperthermia susceptibility (MHS) is an autosomal dominant pharmacogenetic disorder that manifests as a hypermetabolic state when carriers are exposed to halogenated volatile anesthetics or depolarizing muscle relaxants. In animals, heat stress intolerance is also observed. MHS is linked to over 40 variants in RYR1 that are classified as pathogenic for diagnostic purposes. More recently, a few rare variants linked to the MHS phenotype have been reported in CACNA1S, which encodes the voltage-activated Ca²⁺ channel Ca_V1.1 that conformationally couples to RyR1 in skeletal muscle. Here, we describe a knock-in mouse line that expresses one of these putative variants, Ca_V1.1-R174W. Heterozygous (HET) and homozygous (HOM) Ca_V1.1-R174W mice sur

SUBMITTER: Feng W 

PROVIDER: S-EPMC10413282 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature