Type 1 ryanodine receptor (RyR1) is a Ca²⁺ release channel in the sarcoplasmic reticulum (SR) of the skeletal muscle and plays a critical role in excitation-contraction coupling. Mutations in RyR1 hyperactivate the channel to cause malignant hyperthermia (MH). MH is a serious complication characterized by skeletal muscle rigidity and elevated body temperature in response to commonly used inhalational anesthetics. Recently we generated an MH model (R2509C-RyR1 mice) carrying a p.R2509C mutation in RYR1 using the CRISPR/Cas9 system. In R2509C-RyR1 heterozygous mice, MH-like episodes were induced by volatile anesthetics as well as by an increase in environmental temperature. Also, Fluorescence Ca²⁺ imaging using the endoplasmic reticulum-targeted fluorescent probes demonstrates that the Ca²⁺transients from “Heat-Induced Ca²⁺ Release (HICR)” through RyR1 mutant channels because of the channels’ heat hypersensitivity. We propose that HICR accelerates thermogenesis in patients with MH.