RYR1 and Malignant hyperthermia: In the previous study, we found all three amino acid mutations impaired Ca2+ and Mg2+ inhibition of RyR1 (7); therefore, one possible explanation is that the mutant RyR1s are less suppressed at both resting and activating states, resulting in the enhanced Ca2+- and caffeine-dependent muscle contractions, which are often observed in biopsies from the malignant hyperthermia susceptible patients.