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Updated: Aug 10, 2026

Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Malignant hyperthermia: an inherited disorder of skeletal muscle Ca+ regulation
C F Louis1, E M Balog, B R Fruen
1Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis 55455, USA. louis003@tc.umn.edu
Abstract:
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle characterized by muscle contracture and life-threatening hypermetabolic crisis following exposure to halogenated anesthetics and depolarizing muscle relaxants during surgery. Susceptibility to MH results from mutations in Ca2+ channel proteins that mediate excitation-contraction (EC) coupling, with the ryanodine receptor Ca2+ release channel (RyRI) representing the major locus. Here we review recent studies characterizing the effects of MH mutations on the sensitivity of the RyRI to drugs and endogenous channel effectors including Ca2+ and calmodulin. In addition, we present a working model that incorporates these effects of MH mutations on the isolated RyRI with their effects on the physiologic mechanism that activates Ca2+ release during EC coupling in intact muscle.
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