RYR2 and hereditary disease: In particular, LYC increased Ca2+ transient amplitude and promoted Ca2+ sparks reflecting RyR2-mediated diastolic Ca2+ leakiness responsible for the spontaneous firing of abnormal Ca2+ waves as found in inherited diseases related to RyR2 mutations, chronic diseases such as HF, or adverse drug effects16, 17, 18, 31, 32, 33, 34, 35.