Differential conditions for early after-depolarizations and triggered activity in cardiomyocytes derived from transgenic LQT1 and LQT2 rabbits

摘要

Non-technical summaryLong QT syndrome (LQTS) is a genetic disorder characterized by recurrent syncope and sudden cardiac death (SCD). Type 1 (LQT1) and Type 2 (LQT2) LQTS account for 90% of the genotyped mutations in patients with this disorder. These syndromes have been associated with different sympathetic modes for initiation of cardiac arrest. Using isolated cardiomyocytes and Langendorff-perfused hearts from transgenic rabbit models of LQT1 and LQT2, we have identified differential conditions and cellular mechanisms for the generation of early afterdepolarizations (EADs), abnormal depolarizations during the plateau and repolarization phase of action potentials and the hallmark of the arrhythmias in LQTS. These differences explain why different types of increased autonomic nervous system activity, i.e. sympathetic surge vs. high sympathetic tone, are associated with the initiation of polymorphic ventricular tachycardia in LQTS patients with different genetic background.