Stoichiometry of the KCNQ1-KCNE1 ion channel complex
Stoichiometry of the KCNQ1-KCNE1 ion channel complex
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DOI：
10.1073/pnas.1010354107
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发表时间：
2010-11-02
影响因子：
11.1
通讯作者：
Isacoff, Ehud Y.
中科院分区：
文献类型：
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作者：
Nakajo, Koichi;Ulbrich, Maximilian H.;Isacoff, Ehud Y.
KCNQ 1电压门控钾通道及其辅助亚基KCNE 1在心跳的调节中起着至关重要的作用。KCNQ 1和KCNE 1复合物的化学计量一直存在争议，一些结果表明，形成通道的四个KCNQ 1亚基与两个KCNE 1亚基（4：2化学计量）相关联，而其他人则认为化学计量可能不是固定的。我们应用单分子荧光漂白方法来计数许多单个复合物中的亚基，并发现KCNQ 1-KCNE 1复合物的化学计量是灵活的，最多有四个KCNE 1亚基与通道的四个KCNQ 1亚基相关联（4：4化学计量）。发现各种化学计量的比例取决于KCNQ 1和KCNE 1的相对表达密度。引人注目的是，门控的电压依赖性和动力学都被发现依赖于KCNQ 1和KCNE 1的相对密度，这表明心脏节律可能受到辅助亚基的相对表达和由此产生的通道复合物的化学计量的调节。
The KCNQ1 voltage-gated potassium channel and its auxiliary subunit KCNE1 play a crucial role in the regulation of the heartbeat. The stoichiometry of KCNQ1 and KCNE1 complex has been debated, with some results suggesting that the four KCNQ1 subunits that form the channel associate with two KCNE1 subunits (a 4: 2 stoichiometry), while others have suggested that the stoichiometry may not be fixed. We applied a single molecule fluorescence bleaching method to count subunits in many individual complexes and found that the stoichiometry of the KCNQ1 - KCNE1 complex is flexible, with up to four KCNE1 subunits associating with the four KCNQ1 subunits of the channel (a 4: 4 stoichiometry). The proportion of the various stoichiometries was found to depend on the relative expression densities of KCNQ1 and KCNE1. Strikingly, both the voltage-dependence and kinetics of gating were found to depend on the relative densities of KCNQ1 and KCNE1, suggesting the heart rhythm may be regulated by the relative expression of the auxiliary subunit and the resulting stoichiometry of the channel complex.