Wolf Cordula M, Berul Charles I
Department of Cardiology, Children's Hospital, Boston Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
J Cardiovasc Electrophysiol. 2006 Apr;17(4):446-55. doi: 10.1111/j.1540-8167.2006.00427.x.
The cardiac conduction system can be anatomically, developmentally, and molecularly distinguished from the working myocardium. Abnormalities in cardiac conduction can occur due to a variety of factors, including developmental and congenital defects, acquired injury or ischemia of portions of the conduction system, or less commonly due to inherited diseases that alter cardiac conduction system function. So called "idiopathic" conduction system degeneration may have familial clustering, and therefore is consistent with a hereditary basis. This "Molecular Perspectives" will highlight several diverse mechanisms of isolated conduction system disease as well as conduction system degeneration associated with other cardiac and non-cardiac disorders. The first part of this review focuses on channelopathies associated with conduction system disease. Human genetic studies have identified mutations in the sodium channel SCN5A gene causing tachyarrhythmia disorders, as well as progressive cardiac conduction system diseases, or overlapping syndromes. Next, the importance of embryonic developmental genes such as homeobox and T-box transcription factors are highlighted in conduction system development and function. Conduction system diseases associated with multisystem disorders, such as muscular and myotonic dystrophies, will be described. Last, a new glycogen storage cardiomyopathy associated with ventricular preexcitation and progressive conduction system degeneration will be reviewed. There are a myriad of mutations identified in genes encoding cardiac transcription factors, ion channels, gap junctions, energy metabolism regulators, lamins and other structural proteins. Understanding of the molecular and ionic mechanisms underlying cardiac conduction is essential for the appreciation of the pathogenesis of conduction abnormalities in structurally normal and altered hearts.
心脏传导系统在解剖学、发育学和分子层面上可与工作心肌区分开来。心脏传导异常可由多种因素引起，包括发育和先天性缺陷、传导系统部分区域的后天损伤或缺血，或较少见的由改变心脏传导系统功能的遗传性疾病引起。所谓的“特发性”传导系统退变可能存在家族聚集性，因此符合遗传基础。这篇“分子视角”文章将重点介绍孤立性传导系统疾病以及与其他心脏和非心脏疾病相关的传导系统退变的几种不同机制。本综述的第一部分聚焦于与传导系统疾病相关的离子通道病。人类遗传学研究已确定，钠通道SCN5A基因的突变会导致快速性心律失常疾病，以及进行性心脏传导系统疾病或重叠综合征。接下来，将强调胚胎发育基因如同源盒和T盒转录因子在传导系统发育和功能中的重要性。还将描述与多系统疾病相关的传导系统疾病，如肌肉和强直性肌营养不良。最后，将综述一种与心室预激和进行性传导系统退变相关的新型糖原贮积性心肌病。在编码心脏转录因子、离子通道、缝隙连接、能量代谢调节因子、核纤层蛋白和其他结构蛋白的基因中已发现无数突变。了解心脏传导的分子和离子机制对于理解结构正常和改变的心脏中传导异常的发病机制至关重要。
