Oh Seunghoon, Bargiello Thaddeus A
Department of Physiology, College of Medicine, Dankook University, Cheonan, Korea.
Dominic P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
Yonsei Med J. 2015 Jan;56(1):1-15. doi: 10.3349/ymj.2015.56.1.1.
Voltage is an important parameter that regulates the conductance of both intercellular and plasma membrane channels (undocked hemichannels) formed by the 21 members of the mammalian connexin gene family. Connexin channels display two forms of voltage-dependence, rectification of ionic currents and voltage-dependent gating. Ionic rectification results either from asymmetries in the distribution of fixed charges due to heterotypic pairing of different hemichannels, or by channel block, arising from differences in the concentrations of divalent cations on opposite sides of the junctional plaque. This rectification likely underpins the electrical rectification observed in some electrical synapses. Both intercellular and undocked hemichannels also display two distinct forms of voltage-dependent gating, termed Vj (fast)-gating and loop (slow)-gating. This review summarizes our current understanding of the molecular determinants and mechanisms underlying these conformational changes derived from experimental, molecular-genetic, structural, and computational approaches.
电压是调节由哺乳动物连接蛋白基因家族的21个成员形成的细胞间通道和质膜通道(未对接的半通道)电导的重要参数。连接蛋白通道表现出两种电压依赖性形式,即离子电流的整流和电压依赖性门控。离子整流要么是由于不同半通道的异型配对导致固定电荷分布不对称,要么是由于连接斑两侧二价阳离子浓度差异引起的通道阻断。这种整流可能是一些电突触中观察到的电整流的基础。细胞间通道和未对接的半通道也都表现出两种不同形式的电压依赖性门控,称为Vj(快速)门控和环(慢速)门控。本综述总结了我们目前对这些构象变化的分子决定因素和机制的理解,这些理解来自实验、分子遗传学、结构和计算方法。