A novel RyR1 inhibitor prevents and rescues sudden death in a mouse model of malignant hyperthermia and heat stroke

• Published in: bioRxiv
• Main Authors: Yamazawa, Toshiko, Kobayashi, Takuya, Kurebayashi, Nagomi, Konishi, Masato, Noguchi, Satoru, Inoue, Takayoshi, Inoue, Yukiko U, Nishino, Ichizo, Mori, Shuichi, Iinuma, Hiroto, Manaka, Noriaki, Kagechika, Hiroyuki, Uryas, Arkady, Adams, Jose, Lopez, Jose R, Liu, Xiaochen, Diggle, Christine, Allen, Paul D, Kakizawa, Sho, Ikeda, Keigo, Lin, Bangzhong, Ikemi, Yui, Nunomura, Kazuto, Nakagawa, Shinsaku, Sakurai, Takashi, Murayama, Takashi
• Format: Paper
• Language: English; Japanese
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 06.02.2021
• Subjects: Anesthesia; Animal models; Caffeine; Calcium (intracellular); Calcium release channels; Carboxylic acids; Halothane; Heat; Heatstroke; Hyperthermia; Isoflurane; Malignant hyperthermia; Musculoskeletal system; Mutation; Ryanodine receptors; Skeletal muscle; Solubility

Abstract Mutations in the type 1 ryanodine receptor (RyR1), a Ca2+ release channel in skeletal muscle, hyperactivate the channel to cause malignant hyperthermia (MH) and are implicated in severe heat stroke. Dantrolene, the only approved drug for MH, has the disadvantages of having very poor water s...