Molecular mechanisms underlying membrane-potential-mediated regulation of neuronal K2P2.1 channels
Molecular mechanisms underlying membrane-potential-mediated regulation of neuronal K2P2.1 channels
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DOI：
10.1016/j.mcn.2009.10.002
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发表时间：
2010-01
影响因子：
3.5
通讯作者：
Yifat Segal-Hayoun;Asi Cohen;N. Zilberberg
中科院分区：
文献类型：
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作者：
Yifat Segal-Hayoun;Asi Cohen;N. Zilberberg
背景K2 P通道的活性调节静息膜电位，使可兴奋细胞具有可塑性。本文研究了静息膜电位对神经元人K2P2.1（KCNK 2，TREK-1）通道活性的调节。当在非洲爪蟾卵母细胞中异源表达时，K2 P 2.1电流在超极化电位下逐渐增加数倍，在去极化电位下下降数倍，中点电位为− 60 mV。由于K2 P通道没有配备一个完整的电压传感器，我们寻找外源性细胞成分，可以转换膜电场的变化，细胞活性，间接修改K2 P 2.1电流。K2 P 2.1电压敏感性不受电压激活的钙通道、爪蟾电压敏感性质子通道（Xl-Hv）或爪蟾电压传感器磷酸酶（Xl-VSP）的活性介导。另一方面，我们报道了在明显缺乏配体的情况下，膜去极化激活了Gq蛋白偶联受体途径，通过磷脂酶C的作用导致磷脂酰肌醇-4，5-二磷酸（PIP 2）耗尽。我们的研究结果提出了一种新的机制，其中间接途径赋予膜电位调节通道，本质上不是电压敏感的，以提高神经元兴奋性水平的调节。这些蛋白质在没有任何外部配体的情况下运作的能力增强了单细胞水平的可塑性，不依赖于组织甚至生物体水平的更高调节途径。
The activity of background K 2P channels adjusts the resting membrane potential to enable plasticity of excitable cells. Here we have studied the regulation of neuronal human K 2P 2.1 (KCNK2, TREK-1) channel activity by resting membrane potential. When heterologously expressed in Xenopus laevis oocytes, K 2P 2.1 currents gradually increased several fold at hyperpolarizing potentials and declined several fold at depolarizing potentials, with a midpoint potential of− 60 mV. As K 2P channels are not equipped with an integral voltage sensor, we sought extrinsic cellular components that could convert changes in the membrane electrical field to cellular activity that would indirectly modify K 2P 2.1 currents. K 2P 2.1 voltage sensitivity was found not to be mediated by the activity of either voltage activated calcium channels, the Xenopus voltage sensitive proton channel (Xl-Hv) or the Xenopus voltage sensor-containing phosphatase (Xl-VSP). On the other hand, we report that membrane depolarization activated the Gq protein-coupled receptor pathway, in the apparent absence of ligand, resulting in phosphatidylinositol-4, 5-bisphosphate (PIP 2) depletion through the action of phospholipase C. Our results suggest a novel mechanism in which an indirect pathway confers membrane potential regulation onto channels that are not intrinsically voltage-sensitive to enhance regulation of neuronal excitability levels. The ability of these proteins to operate without any external ligand enhances plasticity at the single cell level, independent of higher regulatory pathways at the tissue or even the organism levels.