Activation of a mechanosensitive BK channel by membrane stress created with amphipaths
Activation of a mechanosensitive BK channel by membrane stress created with amphipaths
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通过两性分子产生的膜应力激活机械敏感 BK 通道
DOI：
10.1080/09687860500370703
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发表时间：
2005-11-01
影响因子：
--
通讯作者：
Sokabe, M
中科院分区：
文献类型：
--
作者：
Qi, Z;Chi, SP;Sokabe, M
一些BK通道在膜拉伸时被激活。然而，目前尚不清楚是哪种膜组分将力传递给通道，以及通道的哪一部分感知到力。最近，我们已经证明从鸡心脏克隆的BK通道（命名为SAKCa通道）是一个拉伸激活通道，而位于细胞质侧的59个氨基酸剪接插入（STREX）的缺失，消除了它的拉伸敏感性。这一发现提出了一个问题，即双分子层中的应力是否对通道的机械激活至关重要。为了解决这个问题，我们研究了膜扰动双通路对SAKCa通道及其strex缺失突变体拉伸激活的影响。我们发现阴离子两路三硝基苯酚（TNP）和阳离子两路氯丙嗪（CPZ）在单独应用时都可以通过向左移动电压激活曲线来剂量依赖性地激活通道。相比之下，TNP和CPZ在顺序施用时相互补偿。这些结果可以在双层偶联假说的框架下理解，表明质膜中的应力可以激活SAKCa通道。有趣的是，STREX缺失突变通道对两路通路的敏感性要低得多，这表明STREX作为一种中间结构，可以通过一种未知的膜相关蛋白间接将膜中的应激传递到SAKCa通道的门，该蛋白可以检测或传递膜中的应激。
Some BK channels are activated in response to membrane stretch. However, it remains largely unknown which membrane component transmits forces to the channel and which part of the channel senses the force. Recently, we have shown that a BK channel cloned from chick heart (named SAKCa channel) is a stretch activated channel, while deletion of a 59 amino acids splice insert (STREX) located in the cytoplasmic side, abolishes its stretch-sensitivity. This finding raised a question whether stress in the bilayer is crucial for the mechanical activation of the channel. To address this question we examined the effects of membrane perturbing amphipaths on the stretch activation of the SAKCa channel and its STREX-deletion mutant. We found that both anionic amphipath trinitrophenol (TNP) and cationic amphipath chlorpromazine (CPZ) could dose-dependently activate the channel by leftward shifting the voltage activation curve when applied alone. In contrast, TNP and CPZ compensated each other's effect when applied sequentially. These results can be understood in the framework of the bilayer couple hypothesis, suggesting that stress in the plasma membrane can activate the SAKCa channel. Interestingly, the STREX-deletion mutant channel has much less sensitivity to the amphipaths, suggesting that STREX acts as an intermediate structure that can indirectly convey stress in the membrane to the gate of the SAKCa channel via an unidentified membrane associated protein(s) that can detect or transmit stress in the membrane.