Cerrone Marina, Delmar Mario
Leon H. Charney Division of Cardiology, New York University School of Medicine, 522 First Avenue, SRB 806, New York, NY 10016.
Leon H. Charney Division of Cardiology, New York University School of Medicine, 522 First Avenue, SRB 806, New York, NY 10016.
Trends Cardiovasc Med. 2014 Jul;24(5):184-90. doi: 10.1016/j.tcm.2014.02.001. Epub 2014 Feb 22.
Mutations in proteins of the desmosome are associated with arrhythmogenic cardiomyopathy (AC; also referred to as "ARVC" or "ARVD"). Life-threatening ventricular arrhythmias often occur in the concealed phase of the disease before the onset of structural changes. Among the various potential mechanisms for arrhythmogenesis in AC, in this article, we concentrate on the relation between desmosomes and sodium channel function. We review evidence indicating that (1) loss of desmosomal integrity (including mutations or loss of expression of plakophilin-2; PKP2) leads to reduced sodium current (INa), (2) the PKP2-INa relation could be partly consequent to the fact that PKP2 facilitates proper trafficking of proteins to the intercalated disc, and (3) PKP2 mutations can be present in patients diagnosed with Brugada syndrome (BrS), thus supporting the previously proposed notion that AC and BrS are not two completely separate entities, but "bookends" in a continuum of variable sodium current deficiency and structural disease.
桥粒蛋白的突变与致心律失常性心肌病（AC；也称为“致心律失常性右室心肌病”或“ARVD”）相关。危及生命的室性心律失常常在疾病的隐匿期发生，此时结构改变尚未出现。在AC心律失常发生的各种潜在机制中，在本文中，我们着重探讨桥粒与钠通道功能之间的关系。我们回顾了相关证据，表明（1）桥粒完整性丧失（包括盘状球蛋白2；PKP2的突变或表达缺失）导致钠电流（INa）降低，（2）PKP2与INa的关系可能部分归因于PKP2促进蛋白质向闰盘的正常转运这一事实，以及（3）被诊断为Brugada综合征（BrS）的患者可能存在PKP2突变，从而支持了先前提出的观点，即AC和BrS并非两个完全独立的实体，而是可变钠电流缺乏和结构疾病连续体中的“两端”。
