Tuning the mechanosensitivity of a BK channel by changing the linker length
Tuning the mechanosensitivity of a BK channel by changing the linker length
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通过改变链接器长度来调整 BK 通道的机械敏感性
DOI：
10.1038/cr.2008.88
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发表时间：
2008-08-01
期刊：
影响因子：
44.1
通讯作者：
Sokabe, Masahiro
中科院分区：
文献类型：
--
作者：
Zhao, Hucheng;Sokabe, Masahiro
一些大电导 Ca 2+ 和电压激活的 K+(BK) 通道可通过膜拉伸激活。然而，BK 通道的机械门控机制仍不清楚。先前的研究提出，连接体-门控环复合体起到被动弹簧的作用，将细胞内Ca 2+ 产生的力传递到门以打开通道。这就提出了一个问题：膜拉伸是否也通过连接子门控复合物传递到机械敏感 (MS) BK 通道的门控。为了研究这一点，我们改变了拉伸激活的 BK 通道 (SAKCaC) 中的接头长度，并检查了膜拉伸对所得突变体通道门控的影响。在细胞内Ca 2+ 存在和不存在的情况下，缩短连接体都会增加通道机械敏感性，而延长连接体则会降低通道机械敏感性。然而，电压和Ca 2+ 敏感性并未因膜拉伸而显着改变。此外，SAKCaC 在相对较高的细胞内 Ca 2+ 浓度或膜去极化下对膜拉伸变得不太敏感。这些观察结果表明，一旦通道处于开放状态构象，弹簧上的张力就会部分释放，膜拉伸的效果就会降低。我们的结果与膜拉伸通过 MS BK 通道的连接体-门控环复合物转移到门的想法是一致的。
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.