Characterization and temporal development of cores in a mouse model of malignant hyperthermia

摘要: Malignant hyperthermia (MH) and central core disease are related skeletal muscle diseases often linked to mutations in the type 1 ryanodine receptor (RYR1) gene, encoding for Ca2+ release channel of sarcoplasmic reticulum (SR). In humans, Y522S RYR1 mutation is associated with malignant susceptibility (MHS) presence fibers regions that lack mitochondria. heterozygous knock-in mice (RYR1Y522S/WT), causes SR leak MHS. Here, we identified mitochondrial-deficient from RYR1Y522S/WT characterized structural temporal aspects involved their formation. Mitochondrial swelling/disruption, initial detectable change observed young-adult (2 months), does not occur randomly but rather confined discrete areas termed presumptive cores. This localized mitochondrial damage followed by local disruption/loss nearby transverse tubules, resulting early cores (2–4 months) small contracture extreme sarcomere shortening At later stages (1 year), extended, frequent, accompanied which contractile elements also severely compromised (unstructured cores). Based on these observations, propose a possible series events leading formation mice: Initial mitochondrial/SR disruption significant loss sequestration eventually results contractures progressive degradation elements.