Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid bilayers.
Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid bilayers.
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DOI：
10.1016/j.jmb.2008.06.085
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发表时间：
2008-09-26
影响因子：
5.6
通讯作者：
MacKinnon, Roderick
中科院分区：
文献类型：
--
作者：
Tao, Xiao;MacKinnon, Roderick
关键词：
电压依赖性K+通道在可兴奋和非可兴奋细胞中塑造电信号中起关键作用。这些通道响应于跨细胞膜的电压变化而打开和关闭。为了理解电压感测机制，已经进行了许多研究。我们的实验室最近确定了哺乳动物电压依赖性K+通道Kv1.2和Kv1.2的突变体的原子结构命名为'桨嵌合体'通道，其中电压传感器桨从Kv2.1转移到Kv1.2。这两种结构提供了前所未有的清晰度的电压依赖性通道的原子描述。到目前为止，这两个通道的功能完整性在酵母细胞中生物合成尚未进行评估。在这里，我们报告的电生理和药理学特性的Kv1.2和桨嵌合体通道的平面脂质双层。我们表明，毕赤酵母产生“正常运作”的哺乳动物电压依赖性K+通道与定性相似的功能，在没有N-末端失活门的情况下，振动筛K+通道，以及桨状嵌合体突变体通道的功能以及Kv1.2。然而，我们发现，在几个方面的Kv1.2通道具有不同于文献中报道的Kv1.2通道的功能特性。
Voltage-dependent K+ channels play key roles in shaping electrical signaling in both excitable as well as non-excitable cells. These channels open and close in response to the voltage changes across the cell membrane. Many studies have been carried out in order to understand the voltage sensing mechanism. Our laboratory recently determined the atomic structures of a mammalian voltage-dependent K+ channel Kv1.2 and a mutant of Kv1.2 named the ‘paddle-chimera’ channel, in which the voltage sensor paddle was transferred from Kv2.1 to Kv1.2. These two structures provide atomic descriptions of voltage-dependent channels with unprecedented clarity. Until now the functional integrity of these two channels biosynthesized in yeast cells have not been assessed. Here we report the electrophysiological and pharmacological properties of Kv1.2 and the paddle chimera channels in planar lipid bilayers. We demonstrate that Pichia yeast produce ‘normally functioning’ mammalian voltage-dependent K+ channels with qualitatively similar features to the Shaker K+ channel in the absence of the N-terminal inactivation gate, and that the paddle chimera mutant channel functions as well as Kv1.2. We find, however, that in several respects the Kv1.2 channel exhibits functional properties that are distinct from Kv1.2 channels reported in the literature.
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影响因子：
16.2
作者：
Aggarwal, SK;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
64.8
作者：
Ruta, V;Jiang, YX;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
16.2
作者：
Liu, Y;Jurman, ME;Yellen, G
通讯作者：
Yellen, G