RYR2 and Malignant hyperthermia: A clue was provided by Gomez et al. [37] who found that malignant hyperthermia mutations of three amino acids of the S23 loop shifted the inhibition of ryanodine binding in RyR1 to a higher Ca2+ concentration, close to that of the RyR2, and proposed that these three amino acids are involved in the inter-monomeric interaction of the S23* loop with the EF-hand region [37].