首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Participation of the S4 voltage sensor in the Mg2+-dependent activation of large conductance (BK) K+ channels.
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Participation of the S4 voltage sensor in the Mg2+-dependent activation of large conductance (BK) K+ channels.

机译:S4电压传感器参与Mg2 +依赖性大电导(BK)K +通道的激活。

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摘要

The S4 transmembrane segment is the primary voltage sensor in voltage-dependent ion channels. Its movement in response to changes in membrane potential leads to the opening of the activation gate, which is formed by a separate structural component, the S6 segment. Here we show in voltage-, Ca2+-, and Mg2+-dependent, large conductance K+ channels that the S4 segment participates not only in voltage- but also Mg2+-dependent activation. Mutations in S4 and the S4-S5 linker alter voltage-dependent activation and have little or no effect on activation by micromolar Ca2+. However, a subset of these mutations in the C-terminal half of S4 and in the S4-S5 linker either reduce or abolish the Mg2+ sensitivity of channel gating. Cysteine residues substituted into positions R210 and R213, marking the boundary between S4 mutations that alter Mg2+ sensitivity and those that do not, are accessible to a modifying reagent [sodium (2-sulfonatoethyl)methane-thiosulfonate] (MTSES) from the extracellular and intracellular side of the membrane, respectively, at -80 mV. This implies that interactions between S4 and a cytoplasmic domain may be involved in Mg2+-dependent activation. These results indicate that the voltage sensor is critical for Mg2+-dependent activation and the coupling between the voltage sensor and channel gate is a converging point for voltage- and Mg2+-dependent activation pathways.
机译:S4跨膜段是依赖电压的离子通道中的主要电压传感器。其响应于膜电势变化的运动导致激活门的打开,该激活门由单独的结构组件S6段形成。在这里,我们在依赖电压,Ca2 +和Mg2 +的大电导K +通道中显示S4段不仅参与电压依赖的活化,而且参与Mg2 +依赖的活化。 S4和S4-S5接头的突变会改变电压依赖性激活,对微摩尔Ca2 +的激活几乎没有影响。但是,在S4的C末端一半和S4-S5接头中的这些突变的子集会降低或消除通道门控的Mg2 +敏感性。半胱氨酸残基被替换为位置R210和R213,标志着改变Mg2 +敏感性的S4突变与不改变Mg2 +敏感性的S4突变之间的边界,可通过细胞外和细胞内的修饰剂[(2-磺基乙基)甲烷-硫代磺酸钠](MTSES)进入膜的侧面分别为-80 mV。这意味着S4和胞质域之间的相互作用可能参与了Mg2 +依赖性激活。这些结果表明,电压传感器对于依赖Mg2 +的激活至关重要,并且电压传感器与通道栅极之间的耦合是依赖电压和Mg2 +的激活路径的汇聚点。

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