The search is on for the voltage sensor-to-gate coupling.

The search is on for the voltage sensor-to-gate coupling.
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DOI:
10.1085/jgp.20028657
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发表时间:
2002-10
期刊:
The Journal of general physiology
影响因子:
--
通讯作者:
Larsson HP
Larsson HP
中科院分区:
其他
文献类型:
--
作者:
Larsson HP

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Hodgkin和Huxley(1952)证明了电压激活的钠(Na)和钾(K)渗透性存在于鱿鱼巨大的轴突中。从那以后,生物物理学家们一直试图了解电压是如何激活负责动作电位的离子通路的。Hodgkin和Huxley(1952)得出结论,膜中必须存在电荷或电荷偶极子,它们会随着膜上电压的变化而移动,从而打开或关闭Na和K的渗透率。我们现在知道Na和K离子通过电压激活的Na和K通道。这些电压激活的离子通道由:(a)包含离子渗透途径和控制离子流动的门的孔隙形成域,(b)包含电压传感器的电压传感域,以及(c)将电压传感器连接到孔中的门的耦合机制组成(图1)。自从霍奇金和赫胥黎的第一个电压钳实验以来,我们对离子通道如何工作的理解已经走了很长一段路。然而,我们仍然不完全了解电压变化如何打开和关闭这些通道的分子机制,并且我们对电压传感器和栅极之间的耦合机制知之甚少。在这个观点中,我给出了我对电压激活的K (Kv)通道和密切相关的离子通道(电压门控和电压无关离子通道)中门控的分子机制的看法。
Hodgkin and Huxley (1952) demonstrated the presence of voltage-activated sodium (Na) and potassium (K) permeabilities in the squid giant axon. Ever since then, biophysicists have tried to understand how voltage activates the ionic pathways responsible for the action potential. Hodgkin and Huxley (1952) concluded that there had to be charges or charge dipoles in the membrane that move in response to changes in the voltage across the membrane, turning the Na and K permeabilities on and off. We now know that Na and K ions go through voltage-activated Na and K channels. These voltage-activated ion channels are composed of:(a) a pore-forming domain that contains the ion permeation pathway and the gates that control the flow of ions,(b) a voltage-sensing domain that contains the voltage sensor, and (c) a coupling mechanism that links the voltage sensor to the gates in the pore (Fig. 1). We have come a long way in our understanding of how ion channels work since Hodgkin and Huxley’s first voltage-clamp experiments. However, we still do not fully understand the molecular mechanism of how changes in voltage open and close these channels, and, we know even less about the coupling mechanism between the voltage sensors and the gates. In this Perspective, I give my view of the molecular mechanism of gating in voltage-activated K (Kv) channels and closely related ion channels (both voltage-gated and voltageindependent ion channels).
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