摘要
一些大传导力的 Ca2+ 和激活电压的 K+( 放射性元素) 隧道被膜段激活。然而, BK 隧道的门 mechano 的机制仍然不好被理解。以前的研究导致了连接器门戒指建筑群作为一个被动弹簧工作的建议,力量由细胞内部的 Ca2+ 产生了到门打开隧道的 transducing。这提出膜段是否也被传给 mechanosensitive (MS ) 的门的问题经由连接器门建筑群的放射性元素隧道。学习这,我们在激活段的放射性元素隧道(SAKCaC ) 改变了连接器长度,并且在结果的变异的隧道的 gating 上检验了膜段的效果。弄短而扩大连接器,增加的连接器减少了,隧道 mechanosensitivity 当面并且当细胞内部的 Ca2+ 不在时。然而,电压和 Ca2+ 敏感没被膜段显著地改变。而且, SAKCaC 在相对高的细胞内部的 Ca2+ 集中或膜去极对膜段变得不太敏感。这些观察建议一旦隧道在开状态的符合构造,在春天的紧张部分被释放,膜段是不太有效的。我们的结果与那膜段经由 MS 放射性元素隧道的连接器门戒指建筑群被转移到门的想法一致。
Some large-conductance Ca^2+ and voltage-activated K^+(BK) channels are activated by membrane stretch. However, the mechanism of mechano-gating of the BK channels is still not well understood. Previous studies have led to the proposal that the linker-gating ring complex functions as a passive spring, transducing the force generated by intracellular Ca^2+ to the gate to open the channel. This raises the question as to whether membrane stretch is also transmitted to the gate of mechanosensitive (MS) BK channels via the linker-gating complex. To study this, we changed the linker length in the stretch-activated BK channel (SAKCaC), and examined the effect of membrane stretch on the gating of the resultant mutant channels. Shortening the linker increased, whereas extending the linker reduced, the channel mechanosensitivity both in the presence and in the absence of intracellular Ca^2+. However, the voltage and Ca^2+ sensitivities were not significantly altered by membrane stretch. Furthermore, the SAKCaC became less sensitive to membrane stretch at relatively high intracellular Ca^2+ concentrations or membrane depolarization. These observations suggest that once the channel is in the open-state conformation, tension on the spring is partially released and membrane stretch is less effective. Our results are consistent with the idea that membrane stretch is transferred to the gate via the linker-gating ring complex of the MS BK channels.
基金
Acknowledgments We thank Ms Mekie Takahashi, Ms Ritsuko Kanda (Nagaya University, Japan), Dr Changliang Fu and Dr Shouqing Lu (Institute of Mechanics, Chinese Academy of Sciences) for technical assistance. This work was partly supported by research grants from the National Natural Science Foundation of China (10602031) and Grants-in-aid for Scientific Research on Priority Areas (#15086270 to M.S.) and Creative Research (# 16GS0308 to M.S.) from the Ministry of Education Science Sports and Culture, Japan.
关键词
BK信道
心脏疾病
连接程序
变换过程
BK channel, mechanosensitive channel, mechano-gating, heart