Cardiac pathophysiology 927

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(n=6): 3.5±0.5; p

Cardiac pathophysiology

myofilaments was increased. However, the underlying mechanism by which the cTnT mutations lead to lethal arrhythmia and the possibility of developing a therapeutic strategy against lethal arrhythmia remains elusive. Here, we hypothesized that aberrant Ca2+ release via the cardiac ryanodine receptor (RyR2) could be altered arrhythmogenesis in FHC. To verify this hypothesis, we investigated the pathogenic role of aberrant Ca2+ release and the therapeutic effects of Dantrolene, which was found to correct the defective inter-domain interaction of RyR2 in catecholaminergic polymorphic ventricular tachycardia and failing hearts (i.e. unzipping to zipping) in transgenic mouse (TG) model with FHC-related cTnT mutation (delta160E). Methods and results: In 6thmonth-old TG, there was no appreciable difference in the structural or functional features of the hearts between non-TG mice and TG. In response to isoproterenol (ISO; 10 nmol/L), the Ca2+ spark frequency was much higher in TG cardiomyocytes than in non-TG {TG (n=7): 7.9±0.6; non-TG (n=6): 3.5±0.5; p