Gating the pore of potassium leak channels
Gating the pore of potassium leak channels
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DOI：
10.1007/s00249-009-0457-6
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发表时间：
2009-12-01
影响因子：
2
通讯作者：
Zilberberg, Noam
中科院分区：
文献类型：
--
作者：
Cohen, Asi;Ben-Abu, Yuval;Zilberberg, Noam
钾通道功能的一个关键特征是能够响应细胞或细胞外信号而发生构象变化，从而在传导和非传导状态之间切换。门控域运动与孔打开和关闭的机械耦合促进了这种切换。双孔域钾通道 (K-2P) 传导泄漏或背景钾选择性电流，这些电流大多与时间和电压无关。这些通道在设置细胞静息膜电位方面发挥着重要作用，从而调节细胞的反应性和兴奋性。因此，K-2P 通道是许多生理过程的关键参与者，并且最近被证明也参与人类病理学。众所周知，K-2P 通道电导、开放概率和细胞表面表达受到各种物理和化学刺激的显着调节。然而，在理解这些信号如何转化为打开或关闭通道门的构象变化时，仍然存在更多的悬而未决的问题而不是答案。越来越多的证据表明，外孔区域在门控 K-2P 通道中发挥着关键作用，其方式类似于电压门控钾通道的 C 型失活。在一些 K-2P 通道中，这种门控机制是为了响应外部 pH 水平而促进的。最近，有人提出 K-2P 通道还具有与外孔门正耦合的较低激活门。本综述的目的是提供最新的研究摘要，描述通道调节过程中 K-2P 通道离子传导途径发生的构象变化和门控事件。
A key feature of potassium channel function is the ability to switch between conducting and non-conducting states by undergoing conformational changes in response to cellular or extracellular signals. Such switching is facilitated by the mechanical coupling of gating domain movements to pore opening and closing. Two-pore domain potassium channels (K-2P) conduct leak or background potassium-selective currents that are mostly time- and voltage-independent. These channels play a significant role in setting the cell resting membrane potential and, therefore modulate cell responsiveness and excitability. Thus, K-2P channels are key players in numerous physiological processes and were recently shown to also be involved in human pathologies. It is well established that K-2P channel conductance, open probability and cell surface expression are significantly modulated by various physical and chemical stimuli. However, in understanding how such signals are translated into conformational changes that open or close the channels gate, there remain more open questions than answers. A growing line of evidence suggests that the outer pore area assumes a critical role in gating K-2P channels, in a manner reminiscent of C-type inactivation of voltage-gated potassium channels. In some K-2P channels, this gating mechanism is facilitated in response to external pH levels. Recently, it was suggested that K-2P channels also possess a lower activation gate that is positively coupled to the outer pore gate. The purpose of this review is to present an up-to-date summary of research describing the conformational changes and gating events that take place at the K-2P channel ion-conducting pathway during the channel regulation.