Moreno Alonso P
Krannert Institute of Cardiology, Indiana University School of Medicine, 1800 N. Capitol Ave. Suite 310, Indianapolis, IN 46202, USA.
Cardiovasc Res. 2004 May 1;62(2):276-86. doi: 10.1016/j.cardiores.2004.03.003.
Substantial advances have been made in characterizing the biophysical properties of channels formed exclusively by connexin isoforms expressed mainly in the heart, e.g., Cx43, Cx45 or Cx40. These properties include transjunctional and transmembrane voltage gating as well as their perm-selectivity, chemical gating and, at a single channel level, their multiple open states and changes in mode behavior. Nonetheless, these connexins are rarely expressed individually in a cell and the presence of functional channels constituted by distinct connexin isoforms is now suspected to be a norm. In fact, combinations of the connexins that form heteromeric channels have been described in some tissues, increasing the necessity to reinforce the research that leads to understanding the effects of these heteromeric interaction on the gating and conducting characteristics of the channels. Furthermore, protein-protein interaction studies will help to understand which connexin domains are involved in these interactions and how they affect the physiology of channels and their interaction with other biological and structural molecules in the cell. New information on the biophysical properties of heteromultimeric channels suggests that interaction between connexins and connexons is not as simple as once thought. Theoretically, changes in the coupling of homomeric connexons (Cx43) in the myocardium may not be significant enough to change the physiology of the heart or to incite arrhythmias, but when heteromeric channels are present, alteration in conductance, differential gating sensitivity to bio-gating molecules and changes in voltage sensitivity increase substantially the cell resources to modulate intercellular coupling, which may participate in the physiology and/or pathology of the cardiovascular tissues.
在表征主要由心脏中表达的连接蛋白亚型（如Cx43、Cx45或Cx40）单独形成的通道的生物物理特性方面已经取得了重大进展。这些特性包括跨连接和跨膜电压门控以及它们的通透选择性、化学门控，并且在单通道水平上，还包括它们的多种开放状态和模式行为的变化。然而，这些连接蛋白很少在细胞中单独表达，现在怀疑由不同连接蛋白亚型构成的功能性通道的存在是一种常态。事实上，在一些组织中已经描述了形成异聚体通道的连接蛋白组合，这增加了加强相关研究的必要性，这些研究有助于理解这些异聚体相互作用对通道门控和传导特性的影响。此外，蛋白质-蛋白质相互作用研究将有助于了解哪些连接蛋白结构域参与这些相互作用，以及它们如何影响通道的生理学及其与细胞中其他生物和结构分子的相互作用。关于异源多聚体通道生物物理特性的新信息表明，连接蛋白和连接子之间的相互作用并不像曾经认为的那么简单。从理论上讲，心肌中同源连接子（Cx43）耦合的变化可能不足以显著改变心脏的生理学或引发心律失常，但当存在异聚体通道时，电导的改变、对生物门控分子的差异门控敏感性以及电压敏感性的变化会大大增加细胞调节细胞间耦合的资源，这可能参与心血管组织的生理学和/或病理学过程。
