Potassium K2P ('leak') channels conduct current across the entire physiological voltage range and carry leak or 'background' currents that are, in part, time- and voltage-independent. K2P2.1 channels (i.e., TREK-1, KCNK2) are highly expressed in excitable tissues, where they play a key role in the cellular mechanisms of neuroprotection, anesthesia, pain perception, and depression. Here, we report for the first time that human K2P2.1 channel activity is regulated by monoterpenes (MTs). We found that cyclic, aromatic monoterpenes containing a phenol moiety, such as carvacrol, thymol and 4-IPP had the most profound effect on current flowing through the channel (up to a 6-fold increase). By performing sequential truncation of the carboxyl-terminal domain of the channel and testing the activity of several channel regulators, we identified two distinct regulatory domains within this portion of the protein. One domain, as previously reported, was needed for regulation by arachidonic acid, anionic phospholipids, and temperature changes. Within a second domain, a triple arginine residue motif (R344-346), an apparent PIP2-binding site, was found to be essential for regulation by holding potential changes and important for regulation by monoterpenes.

中文翻译：

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K2P2.1（TREK-1）羧基末端的调节域允许单萜激活通道。

钾K2P（“泄漏”）通道在整个生理电压范围内传导电流，并携带部分或与时间和电压无关的泄漏或“背景”电流。K2P2.1通道（即TREK-1，KCNK2）在兴奋性组织中高度表达，它们在神经保护，麻醉，疼痛感和抑郁的细胞机制中起关键作用。在这里，我们首次报告人类K2P2.1通道活性受单萜（MTs）调控。我们发现，含有苯酚部分的环状芳香单萜，例如香芹酚，百里香酚和4-IPP对流经通道的电流具有最深远的影响（增加了6倍）。通过对通道的羧基末端结构域进行连续的截短并测试几个通道调节剂的活性，我们在蛋白质的这一部分内鉴定了两个不同的调节域。如先前报道的，需要一个域来通过花生四烯酸，阴离子磷脂和温度变化进行调节。在第二个域中，发现了一个三重精氨酸残基基序（R344-346），一个明显的PIP2结合位点，通过保持潜在的变化对调节至关重要，对单萜的调节也很重要。