Ek-Vitorin Jose F, Burt Janis M
Department of Physiology, University of Arizona, Tucson, AZ, USA.
Biochim Biophys Acta. 2013 Jan;1828(1):51-68. doi: 10.1016/j.bbamem.2012.02.003. Epub 2012 Feb 10.
The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore's limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions.
间隙连接通道的开放状态可通过小离子在施加的细胞间（跨连接/跨通道）电压梯度作用下的通透情况得以体现。面对恒定的细胞间电压差，开放的通道允许不同量的电流在细胞间通过，这表明通道的开放/关闭可以是完全的或部分的。这种开放状态选择的生理意义，可以说是连接调节的主要关注点。由于间隙连接对许多物质具有通透性，因此探讨每种开放状态是否以及如何影响与携带电流的离子一样有价值但较难检测的分子的细胞间扩散是合理的。据推测，被视为通道电导率变化的结构改变将显著改变其极限直径接近孔隙极限直径的分子的跨连接扩散。此外，无论是在宏观还是单通道水平，连接对某些分子的通透性变化可能在电导率无明显变化的情况下发生。开放的间隙连接通道通过简单扩散允许接触细胞之间交换细胞质通透物。这些通透物的身份以及它们连接交换的功能情况和后果，目前构成了该领域最紧迫（且要求高）的主题。在这里，我们考虑调节这种交换的必要性、可能涉及的调节机制和结构元件，以及调节现象如何被视为化学偶联与电偶联的变化；然后对我们关于连接通讯的集体知识进行全面反思，以提出新的研究途径。本文是名为“通讯连接、作用和功能障碍”的特刊的一部分。
