Conversely, dantrolene, a specific drug for treatment of malignant hyperthermia, which binds to the RyR2 N-terminal domain (aa 601–620), stabilized the domain-domain interactions from the unzipped to the zipped state, and hence restored normal CaM binding to RyR2, thereby inhibiting Ca2+ leakage in either CPVT-associated RyR2R2474S/+ mouse model9, tachycardia-induced canine heart failure model15, or pressure-overload induced mouse heart failure model18. This evidence concerns the gene RYR2 and heart failure.