Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors
Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors
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DOI：
10.1038/35079500
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发表时间：
2001-06-01
期刊：
影响因子：
64.8
通讯作者：
MacKinnon, R
中科院分区：
文献类型：
--
作者：
Zhou, M;Morais-Cabral, JH;MacKinnon, R
许多电压依赖性K+通道在膜去极化时打开，然后通过称为失活的过程迅速关闭。神经元使用失活的K+通道来调节它们的放电频率。在Shaker型K+通道中，负责通道关闭的失活门由通道的胞质氨基末端形成。在这里，我们表明，中心腔和内孔的K+通道形成的受体网站的失活门和小分子抑制剂。我们提出，失活发生的顺序反应中，门结合最初的细胞质通道表面，然后进入孔作为一个扩展的肽。这一机制解释了K+通道失活的功能特性，并表明空腔可能是某些改变阳离子通道功能的药物的作用部位。
Many voltage-dependent K+ channels open when the membrane is depolarized and then rapidly close by a process called inactivation. Neurons use inactivating K+ channels to modulate their firing frequency. In Shaker-type K+ channels, the inactivation gate, which is responsible for the closing of the channel, is formed by the channel's cytoplasmic amino terminus. Here we show that the central cavity and inner pore of the K+ channel form the receptor site for both the inactivation gate and small-molecule inhibitors. We propose that inactivation occurs by a sequential reaction in which the gate binds initially to the cytoplasmic channel surface and then enters the pore as an extended peptide. This mechanism accounts for the functional properties of K+ channel inactivation and indicates that the cavity may be the site of action for certain drugs that alter cation channel function.