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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Na channel inactivation from open and closed states
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Na channel inactivation from open and closed states

机译：Na通道因打开和关闭状态而失活

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摘要

A sodium channel is composed of four similar domains, each containing a highly charged S4 helix that is driven outward (activates) in response to a depolarization. Functionally, the channel has two gates, called activation gate (a gate) and inactivation gate (I gate), both of which must be open for conduction to occur. The cytoplasmically located a gate opens after a depolarization has activated the S4s of (probably) all four domains. The I gate consists of a cytoplasmically located inactivation "particle" and a receptor for it in the channel. The receptor becomes available after some degree of S4 activation, and the particle diffuses in to inactivate the channel. The I gate usually closes when the a gate is open [open-state inactivation (Osi)] but also can close before the channel reaches the conducting state. This "closed-state inactivation" (Csi) is studied quantitatively in this paper to determine the degree of S4 activation required for (i) opening the a gate, and (h) permitting the I gate to close. Csi is most prominent for small depolarizations, during which occupancy of the partially activated closed states is prolonged. Large depolarizations drive the S4s outward quickly, minimizing the duration of closed-state occupancy and making Csi small and Osi large. Based on these data and evidence in the literature, it is concluded that opening the a gate requires S4 activation in domains 1-3, with partial activation of the S4 of domain 4. Csi requires only S4 activation of domains 3 and 4, which does not open the a gate.
机译：钠通道由四个相似的域组成，每个域都包含一个高电荷S4螺旋，该螺旋响应去极化而被向外驱动（激活）。从功能上讲，该通道具有两个栅极，分别称为激活栅极（一个栅极）和失活栅极（I栅极），这两个栅极必须都打开才能发生导通。去极化激活了（可能）所有四个结构域的S4后，细胞质定位的门打开。 I门由位于细胞质中的失活“颗粒”和其在通道中的受体组成。在一定程度的S4激活后，该受体变得可用，并且粒子扩散进入其中以使通道失活。 I栅极通常在a栅极打开时关闭[open state inactivation（Osi）]，但也可以在通道达到导通状态之前关闭。本文对“关闭状态失活”（Csi）进行了定量研究，以确定（i）打开a栅极和（h）允许I栅极关闭所需的S4激活程度。对于小的去极化，Csi最显着，在此期间，部分激活的闭合状态的占据时间得以延长。较大的去极化将S4迅速向外驱动，从而使闭合状态的持续时间最小化，并使Csi小而Osi大。基于这些数据和文献中的证据，得出的结论是，打开门需要在域1-3中激活S4，部分激活域4的S4。Csi仅需要激活域3和4的S4激活。没有打开一扇门。

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