The role of myocardial gap junctions in electrical conduction and arrhythmogenesis
The role of myocardial gap junctions in electrical conduction and arrhythmogenesis
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DOI：
10.1016/s1054-8807(01)00078-3
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发表时间：
2001-07-01
影响因子：
3.7
通讯作者：
Saffitz, JE
中科院分区：
文献类型：
--
作者：
Kanno, S;Saffitz, JE
心脏的电激活需要通过间隙连接（允许离子和小分子在细胞间通过的密集蛋白质通道阵列）进行细胞间电流转移。由于电流传输仅发生在缝隙连接处，缝隙连接通道的空间分布和生物物理特性是心肌传导特性的重要决定因素。缝隙连接通道由称为连接蛋白的多基因蛋白质家族的成员组成。作为一般规则，单个细胞表达多种连接蛋白，这产生了间隙连接通道相当大的功能多样性的潜力。尽管间隙连接通道对离子和小分子的渗透性相对无选择性，但心肌细胞通过多种机制主动调节其偶联水平，包括连接蛋白表达的变化、连接蛋白运输和周转的调节以及通道特性的调节。在心脏病的晚期，连接蛋白表达和细胞间偶联减少，间隙连接通道重新分布。这些变化与致死性室性心律失常的发病机制密切相关。正在进行的基因工程小鼠的研究揭示了个体间隙连接通道蛋白在正常心脏功能和心肌发生中的作用。(C)2001 Elsevier Science Inc. All rights reserved.
Electrical activation of the heart requires cell-cell transfer of current via gap junctions, arrays of densely packed protein channels that permit intercellular passage of ions and small molecules. Because current transfer occurs only at gap junctions, the spatial distribution and biophysical properties of gap junction channels are important determinants of the conduction properties of cardiac muscle. Gap junction channels are composed of members of a multigene family of proteins called connexins. As a general rule, individual cells express multiple connexins, which creates the potential for considerable functional diversity in gap junction channels. Although gap junction channels are relatively nonselective in their permeability to ions and small molecules, cardiac myocytes actively adjust their level of coupling by multiple mechanisms including changes in connexin expression, regulation of connexin trafficking and turnover, and modulation of channel properties. In advanced stages of heart disease, connexin expression and intercellular coupling are diminished, and gap junction channels become redistributed. These changes have been strongly implicated in the pathogenesis of lethal ventricular arrhythmias. Ongoing studies in genetically engineered mice are revealing insights into the role of individual gap junction channel proteins in normal cardiac function and arrhythmogenesis. (C) 2001 Elsevier Science Inc. All rights reserved.