Excessive Accumulation of Ca^{2 +} in Mitochondria of Y522S-RYR1 Knock-in Mice: A Link Between Leak From the Sarcoplasmic Reticulum and Altered Redox State.

ABSTRACT: Mice (Y522S or YS), carrying a mutation of the sarcoplasmic reticulum (SR) Ca²⁺ release channel of skeletal muscle fibers (ryanodine receptor type-1, RyR1) which causes Ca²⁺ leak, are a widely accepted and intensively studied model for human malignant hyperthermia (MH) susceptibility. Since the involvement of reactive oxygen species (ROS) and of mitochondria in MH crisis has been previously debated, here we sought to determine Ca²⁺ uptake in mitochondria and its possible link with ROS production in single fibers isolated from flexor digitorum brevis (FDB) of YS mice. We found that Ca²⁺ concentration in the mitochondrial matrix, as detected with the ratiometric FRET-based 4mtD3cpv probe, was higher in YS than in wild-type (WT) fibers at rest and a

SUBMITTER: Canato M 

PROVIDER: S-EPMC6755340 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature