CaMKII-mediated phosphorylation of RyR2 plays a crucial role in aberrant Ca2+ release as an arrhythmogenic substrate in cardiac troponin T-related familial hypertrophic cardiomyopathy

Highlights: • We assessed RyR2 phosphorylation in FHC-related TnT-mutated transgenic mice. • The SpF was higher in TG cardiomyocytes than in non-TG cardiomyocytes. • RyR2 was susceptible to CaMKII-mediated phosphorylation due to the mutation. • Increase in diastolic [Ca²⁺]_i caused aberrant Ca²⁺ release and arrhythmia. Cardiac Troponin T (TnT) mutation-linked familial hypertrophic cardiomyopathy (FHC) is known to cause sudden cardiac death at a young age. Here, we investigated the role of the Ca²⁺ release channel of the cardiac sarcoplasmic reticulum (SR), ryanodine receptor (RyR2), in the pathogenic mechanism of lethal arrhythmia in FHC-related TnT-mutated transgenic mice (TG; TnT-delta160E).