Coupling of voltage sensing to channel opening reflects intrasubunit interactions in Kv channels
Coupling of voltage sensing to channel opening reflects intrasubunit interactions in Kv channels
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DOI：
10.1085/jgp.200409194
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发表时间：
2005-01-01
影响因子：
3.8
通讯作者：
Snyders, DJ
中科院分区：
文献类型：
--
作者：
Labro, AJ;Raes, AL;Snyders, DJ
电压门控性K+通道在兴奋性的调节中起核心作用。在这些通道中，电压传感器（主要是S4）的电压依赖性运动耦合到打开渗透路径的（S6）门。由于四聚体结构，这种耦合可以发生在每个亚单元内或相邻亚单元之间。为了区分这些可能性，我们分析了hKv1.5中S4突变（R401N）和S6突变（P511G）的各种组合，将其并入串联构建体以限制亚基化学计量。R401N使激活的电压依赖性向负电位移动，而P511G则相反。当两个突变都引入到串联体的同一个α亚基上时，P511G的正移被R401N的负移所补偿。当每个突变发生在串联的一个单独的亚基上时，这种补偿就不会发生。这表明，对于KV通道，电压感应和门控之间的耦合主要反映了亚基内的相互作用。
Voltage-gated K+ channels play a central role in the modulation of excitability. In these channels, the voltage-dependent movement of the voltage sensor (primarily S4) is coupled to the (S6) gate that opens the permeation pathways Because of the tetrameric structure, such coupling could occur within each subunit or between adjacent subunits. To discriminate between these possibilities, we analyzed various combinations of a S4 mutation (R401N) and a S6 mutation (P511G) in hKv1.5, incorporated into tandem constructs to constrain Subunit stoichiometry. R401N shifted the voltage dependence of activation to negative potentials while P511G did the opposite. When both mutations were introduced in the same a-subunit of the tandem, the Positive shift of P511G was compensated by the negative shift of R401N. With each mutation in a separate subunit of a tandem, this compensation did not occur. This suggests that for Kv channels, the coupling between voltage sensing and gating reflects primarily an intrasubunit interaction.