Nature Communications (Jul 2021)
A novel RyR1-selective inhibitor prevents and rescues sudden death in mouse models of malignant hyperthermia and heat stroke
- Toshiko Yamazawa,
- Takuya Kobayashi,
- Nagomi Kurebayashi,
- Masato Konishi,
- Satoru Noguchi,
- Takayoshi Inoue,
- Yukiko U. Inoue,
- Ichizo Nishino,
- Shuichi Mori,
- Hiroto Iinuma,
- Noriaki Manaka,
- Hiroyuki Kagechika,
- Arkady Uryash,
- Jose Adams,
- Jose R. Lopez,
- Xiaochen Liu,
- Christine Diggle,
- Paul D. Allen,
- Sho Kakizawa,
- Keigo Ikeda,
- Bangzhong Lin,
- Yui Ikemi,
- Kazuto Nunomura,
- Shinsaku Nakagawa,
- Takashi Sakurai,
- Takashi Murayama
Affiliations
- Toshiko Yamazawa
- Department of Molecular Physiology, The Jikei University School of Medicine
- Takuya Kobayashi
- Department of Pharmacology, Juntendo University School of Medicine
- Nagomi Kurebayashi
- Department of Pharmacology, Juntendo University School of Medicine
- Masato Konishi
- Department of Pharmacology, Juntendo University School of Medicine
- Satoru Noguchi
- Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry
- Takayoshi Inoue
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry
- Yukiko U. Inoue
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry
- Ichizo Nishino
- Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry
- Shuichi Mori
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University
- Hiroto Iinuma
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University
- Noriaki Manaka
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University
- Hiroyuki Kagechika
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University
- Arkady Uryash
- Department of Neonatology, Mount Sinai Medical Center
- Jose Adams
- Department of Neonatology, Mount Sinai Medical Center
- Jose R. Lopez
- Department of Research, Mount Sinai Medical Center
- Xiaochen Liu
- Leeds Institute of Biomedical & Clinical Sciences, School of Medicine, University of Leeds, St James’s University Hospital
- Christine Diggle
- Leeds Institute of Biomedical & Clinical Sciences, School of Medicine, University of Leeds, St James’s University Hospital
- Paul D. Allen
- Leeds Institute of Biomedical & Clinical Sciences, School of Medicine, University of Leeds, St James’s University Hospital
- Sho Kakizawa
- Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University
- Keigo Ikeda
- Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Science, Osaka University
- Bangzhong Lin
- Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Science, Osaka University
- Yui Ikemi
- Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Science, Osaka University
- Kazuto Nunomura
- Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Science, Osaka University
- Shinsaku Nakagawa
- Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Science, Osaka University
- Takashi Sakurai
- Department of Pharmacology, Juntendo University School of Medicine
- Takashi Murayama
- Department of Pharmacology, Juntendo University School of Medicine
- DOI
- https://doi.org/10.1038/s41467-021-24644-1
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 14
Abstract
Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.
