Kanno S, Saffitz J E
Department of Surgery and the Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cardiovasc Pathol. 2001 Jul-Aug;10(4):169-77. doi: 10.1016/s1054-8807(01)00078-3.
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.
心脏的电激活需要电流通过缝隙连接进行细胞间传递，缝隙连接是由紧密排列的蛋白质通道组成的阵列，允许离子和小分子在细胞间通过。由于电流传递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。缝隙连接通道由一个称为连接蛋白的多基因家族的成员组成。一般来说，单个细胞表达多种连接蛋白，这使得缝隙连接通道具有相当大的功能多样性。尽管缝隙连接通道对离子和小分子的通透性相对非选择性，但心肌细胞通过多种机制积极调节其偶联水平，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，缝隙连接通道重新分布。这些变化与致命性室性心律失常的发病机制密切相关。对基因工程小鼠的持续研究正在揭示单个缝隙连接通道蛋白在正常心脏功能和心律失常发生中的作用。
