McEwen Dyke P, Martens Jeffrey R
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109-5632, USA.
Mol Interv. 2009 Apr;9(2):79-86. doi: 10.1124/mi.9.2.7.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. The preferred therapy for AF is sustained sinus rhythm control; however, the efficacy of currently used antiarrythmic drugs is limited by adverse side effects resulting from both a lack of ion channel selectivity and nonspecific ventricular activity. The role of the voltage-gated potassium channels in atrial myocyte repolarization and the subsequent control of action potential duration renders them attractive targets for antiarrhythmic drugs in the treatment of AF. Conventional antiarrhythmic drugs generally target the ion permeability of potassium channels. This review discusses the limitations of this traditional approach and introduces, as a novel paradigm for antiarrhythmic pharmacology, the decrease of ion channel cell surface density through the modulation of ion channel trafficking pathways.
心房颤动（AF）是最常见的心律失常。AF的首选治疗方法是维持窦性心律控制；然而，目前使用的抗心律失常药物的疗效受到离子通道选择性缺乏和非特异性心室活动导致的不良副作用的限制。电压门控钾通道在心房肌细胞复极化及随后的动作电位持续时间控制中的作用，使其成为治疗AF的抗心律失常药物的有吸引力的靶点。传统的抗心律失常药物通常靶向钾通道的离子通透性。本文综述讨论了这种传统方法的局限性，并介绍了一种作为抗心律失常药理学新范例的方法，即通过调节离子通道转运途径来降低离子通道细胞表面密度。
