Ordered assembly of the adhesive and electrochemical connections within newly formed intercalated disks in primary cultures of adult rat cardiomyocytes.

Ordered assembly of the adhesive and electrochemical connections within newly formed intercalated disks in primary cultures of adult rat cardiomyocytes.
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DOI:
10.1155/2010/624719
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发表时间:
2010
影响因子:
--
通讯作者:
Russell MW
Russell MW
中科院分区:
其他
文献类型:
--
作者:
Geisler SB;Green KJ;Isom LL;Meshinchi S;Martens JR;Delmar M;Russell MW

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嵌入盘(ID)是一种复杂的结构,它将相邻的心肌细胞电偶联成一个功能syncium。磁盘的完整性对于正常的心脏功能是必不可少的,但是不同的元素是如何组装成一个完全集成的结构还不是很清楚。在这项研究中,我们检测了新id在成年大鼠心肌细胞原代培养中的组装。在分离后2至5天,细胞变平并扩散,建立新的细胞-细胞接触,这种方式再现了心脏发育和心肌重塑过程。当细胞与邻近细胞接触时,跨膜粘附蛋白沿着附着线定位,集中在末端肌节的膜附着部位。Cx43间隙连接和锚蛋白g(电压门控钠通道复合物的基本细胞骨架成分)被二次招募到参与细胞-细胞接触的膜结构域。装配过程的一致顺序表明,对磁盘的机械和电化学元件的集成有特定的脚手架要求。定义作为椎间盘组合基础的关系对于理解伴随ID结构改变的机械功能障碍和心律失常具有重要意义。
The intercalated disk (ID) is a complex structure that electromechanically couples adjoining cardiac myocytes into a functional syncitium. The integrity of the disk is essential for normal cardiac function, but how the diverse elements are assembled into a fully integrated structure is not well understood. In this study, we examined the assembly of new IDs in primary cultures of adult rat cardiac myocytes. From 2 to 5 days after dissociation, the cells flatten and spread, establishing new cell-cell contacts in a manner that recapitulates the in vivo processes that occur during heart development and myocardial remodeling. As cells make contact with their neighbors, transmembrane adhesion proteins localize along the line of apposition, concentrating at the sites of membrane attachment of the terminal sarcomeres. Cx43 gap junctions and ankyrin-G, an essential cytoskeletal component of voltage gated sodium channel complexes, were secondarily recruited to membrane domains involved in cell-cell contacts. The consistent order of the assembly process suggests that there are specific scaffolding requirements for integration of the mechanical and electrochemical elements of the disk. Defining the relationships that are the foundation of disk assembly has important implications for understanding the mechanical dysfunction and cardiac arrhythmias that accompany alterations of ID architecture.
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