Heart Failure Research Center, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Circ Res. 2010 Feb 5;106(2):240-54. doi: 10.1161/CIRCRESAHA.109.205419.
Pacemaker and conduction system myocytes play crucial roles in initiating and regulating the contraction of the cardiac chambers. Genetic defects, acquired diseases, and aging cause dysfunction of the pacemaker and conduction tissues, emphasizing the clinical necessity to understand the molecular and cellular mechanisms of their development and homeostasis. Although all cardiac myocytes of the developing heart initially possess pacemaker properties, the majority differentiates into working myocardium. Only small populations of embryonic myocytes will form the sinus node and the atrioventricular node and bundle. Recent efforts have revealed that the development of these nodal regions is achieved by highly localized suppression of working muscle differentiation, and have identified transcriptional repressors that mediate this process. This review will summarize and reflect new experimental findings on the cellular origin and the molecular control of differentiation and morphogenesis of the pacemaker tissues of the heart. It will also shed light on the etiology of inborn and acquired errors of nodal tissues.
心脏起搏器和传导系统肌细胞在启动和调节心脏腔室收缩方面起着至关重要的作用。遗传缺陷、获得性疾病和衰老导致起搏器和传导组织功能障碍，这强调了深入了解其发育和稳态的分子和细胞机制的临床必要性。尽管心脏发育过程中的所有心肌细胞最初都具有起搏特性，但大多数细胞分化为工作心肌。只有一小部分胚胎心肌细胞将形成窦房结和房室结和束。最近的研究表明，这些节段区域的发育是通过高度局灶性抑制工作肌分化来实现的，并确定了介导这一过程的转录抑制因子。本综述将总结和反映关于心脏起搏器组织的细胞起源和分子调控的新实验发现。它还将阐明先天性和获得性节段组织错误的病因。
