Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
Acta Pharmacol Sin. 2011 Jun;32(6):749-57. doi: 10.1038/aps.2011.44.
Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium (Ca(2+)) from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca(2+) release has been linked to arrhythmogenesis in both the inherited arrhythmia syndrome 'catecholaminergic polymorphic ventricular tachycardia' and acquired forms of heart disease (eg, atrial fibrillation, heart failure). Several classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca(2+) leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modalities based on current evidence of molecular mechanisms.
抗心律失常药物是一组抑制或预防异常心律的药物，异常心律通常与较高的发病率和死亡率有关。目前针对质膜离子通道的抗心律失常药物的临床疗效有限，在某些情况下甚至被描述为致心律失常。然而，最近的研究表明，肌浆网通过心脏兰尼碱受体（RyR2）病理性释放钙（Ca2+）可能成为抗心律失常治疗的一个有希望的靶点。舒张期 SR Ca2+释放与遗传性心律失常综合征“儿茶酚胺多形性室性心动过速”和获得性心脏病（如心房颤动、心力衰竭）的心律失常发生有关。已证实几类药物可降低异常 RyR2 活性，并可通过减少 SR Ca2+泄漏来预防触发心律失常。在这篇综述中，我们将评估稳定 RyR2 的当前药理学方法，并根据目前对分子机制的证据提出治疗方式。
