Sáez Juan C, Retamal Mauricio A, Basilio Daniel, Bukauskas Feliksas F, Bennett Michael V L
Departamento de Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Biochim Biophys Acta. 2005 Jun 10;1711(2):215-24. doi: 10.1016/j.bbamem.2005.01.014. Epub 2005 Mar 2.
Connexins (Cxs) form hemichannels and gap junction channels. Each gap junction channel is composed of two hemichannels, also termed connexons, one from each of the coupled cells. Hemichannels are hexamers assembled in the ER, the Golgi, or a post Golgi compartment. They are transported to the cell surface in vesicles and inserted by vesicle fusion, and then dock with a hemichannel in an apposed membrane to form a cell-cell channel. It was thought that hemichannels should remain closed until docking with another hemichannel because of the leak they would provide if their permeability and conductance were like those of their corresponding cell-cell channels. Now it is clear that hemichannels formed by a number of different connexins can open in at least some cells with a finite if low probability, and that their opening can be modulated under various physiological and pathological conditions. Hemichannels open in different kinds of cells in culture with conductance and permeability properties predictable from those of the corresponding gap junction channels. Cx43 hemichannels are preferentially closed in cultured cells under resting conditions, but their open probability can be increased by the application of positive voltages and by changes in protein phosphorylation and/or redox state. In addition, increased activity can result from the recruitment of hemichannels to the plasma membrane as seen in metabolically inhibited astrocytes. Mutations of connexins that increase hemichannel open probability may explain cellular degeneration in several hereditary diseases. Taken together, the data indicate that hemichannels are gated by multiple mechanisms that independently or cooperatively affect their open probability under physiological as well as pathological conditions.
连接蛋白（Cxs）形成半通道和间隙连接通道。每个间隙连接通道由两个半通道组成，也称为连接子，分别来自两个相连的细胞。半通道是在内质网、高尔基体或高尔基体后区室中组装而成的六聚体。它们通过囊泡运输到细胞表面，并通过囊泡融合插入，然后与相邻膜中的半通道对接形成细胞间通道。人们曾认为，半通道在与另一个半通道对接之前应保持关闭状态，因为如果其通透性和电导率与相应的细胞间通道相似，将会导致泄漏。现在已经清楚，由多种不同连接蛋白形成的半通道在至少某些细胞中能够以一定概率（即使概率很低）打开，并且其打开可在各种生理和病理条件下受到调节。在培养的不同类型细胞中，半通道打开时的电导率和通透性特性可根据相应间隙连接通道预测得出。在静息条件下，Cx43半通道在培养细胞中优先处于关闭状态，但施加正电压以及蛋白质磷酸化和/或氧化还原状态的改变可增加其开放概率。此外，如在代谢受抑制的星形胶质细胞中所见，半通道向质膜募集可导致活性增加。连接蛋白的突变若增加半通道开放概率，可能解释几种遗传性疾病中的细胞变性。综上所述，数据表明半通道由多种机制控制，这些机制在生理和病理条件下独立或协同影响其开放概率。
