Wehrens Xander H T, Lehnart Stephan E, Marks Andrew R
Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Ann N Y Acad Sci. 2005 Jun;1047:366-75. doi: 10.1196/annals.1341.032.
Cardiac arrhythmia is an important cause of death in patients with heart failure (HF) and inherited arrhythmia syndromes, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). Alterations in intracellular calcium handling play a prominent role in the generation of arrhythmias in the failing heart. Diastolic calcium leak from the sarcoplasmic reticulum (SR) via cardiac ryanodine receptors (RyR2) may initiate delayed afterdepolarizations and triggered activity leading to arrhythmias. Similarly, SR Ca(2+) leak through mutant RyR2 channels may cause triggered activity during exercise in patients with CPVT. Novel therapeutic approaches, based on recent advances in the understanding of the cellular mechanisms underlying arrhythmias in HF and CPVT, are currently being evaluated to specifically correct defective Ca(2+) release in these lethal syndromes.
心律失常是心力衰竭（HF）患者以及遗传性心律失常综合征（如儿茶酚胺能多形性室性心动过速（CPVT））患者死亡的重要原因。细胞内钙处理的改变在衰竭心脏心律失常的发生中起重要作用。通过心肌兰尼碱受体（RyR2）从肌浆网（SR）的舒张期钙泄漏可能引发延迟后除极和触发活动，导致心律失常。同样，通过突变的RyR2通道的SR Ca(2+)泄漏可能在CPVT患者运动期间引起触发活动。基于对HF和CPVT中心律失常潜在细胞机制理解的最新进展，目前正在评估新的治疗方法，以特异性纠正这些致死性综合征中缺陷性的Ca(2+)释放。
