The TREK family of leak potassium channels has been found to play critical roles in nociception, sensitivity to general anaesthetics, neuroprotection, and memory. The three members of the family, TREK1, TREK2 and TRAAK establish the resting potential and modify the duration, frequency and amplitude of action potentials. Despite their apparent importance, the repertoire of regulatory interactions utilized by cells to control their expression is poorly understood. Herein, the contribution of miRNAs in the regulation of their post-transcriptional gene expression has been examined. Using different assays, miR-124 and to a lesser extent miR-128 and miR-183 were found to reduce TREK1 and TREK2 levels through specific binding to their 3'UTRs. In contrast, miR-9 which was predicted to bind to TRAAK 3'UTR, did not alter its expression. Expression of miR-124, miR-128 and miR-183 was found to mirror that of Trek1 and Trek2 mRNAs during brain development. Moreover, application of proinflammatory mediators in dorsal root ganglion (DRG) neurons revealed an inverse correlation between miR-124 and Trek1 and Trek2 mRNA expression. Voltage clamp recordings of TREK2-mediated currents showed that miR-124 reduced the sensitivity of TREK2-expressing cells to non-aversive warmth stimulation. Overall, these findings reveal a significant regulatory mechanism by which TREK1 and TREK2 expression and hence activity are controlled in neurons and uncover new druggable targets for analgesia and neuroprotection.Abbreviations: microRNA: miRNA; UTR: untranslated region; K2p channels: two-pore domain K+channels; DRG: dorsal root ganglion; CNS: central nervous system; FBS: fetal bovine serum; TuD: Tough Decoy; TREK: tandem P-domain weak inward rectifying K+ (TWIK)-related K+ channel 1; TRAAK: TWIK-related arachidonic acid K+.

中文翻译：

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神经元microRNA调节TREK两孔域K +通道表达和电流密度。

已经发现TREK泄漏钾通道家族在伤害感受，对全身麻醉剂的敏感性，神经保护和记忆中起关键作用。该家族的三个成员TREK1，TREK2和TRAAK建立了静息电位，并改变了动作电位的持续时间，频率和幅度。尽管它们具有明显的重要性，但人们对细胞用来控制其表达的调节相互作用的全部知识知之甚少。在本文中，已经检查了miRNA在调节其转录后基因表达中的贡献。使用不同的测定方法，发现miR-124和miR-128和miR-183在较小程度上通过与3'UTR特异性结合而降低TREK1和TREK2的水平。相反，预计与TRAAK 3'UTR结合的miR-9不会改变其表达。发现在大脑发育过程中，miR-124，miR-128和miR-183的表达与Trek1和Trek2 mRNA的表达一致。此外，促炎性介质在背根神经节（DRG）神经元中的应用揭示了miR-124与Trek1和Trek2 mRNA表达之间负相关。TREK2介导的电流的电压钳记录表明，miR-124降低了表达TREK2的细胞对非平均温暖刺激的敏感性。总体而言，这些发现揭示了一种重要的调节机制，通过该机制可以控制神经元中TREK1和TREK2的表达，进而控制其活性，并揭示出用于镇痛和神经保护的新药物靶标。UTR：未翻译区域；K2p通道：两孔结构域K +通道；DRG：背根神经节；CNS：中枢神经系统；FBS：胎牛血清；TuD：艰难的诱饵；TREK：串联的P域弱向内整流K +（TWIK）相关的K +通道1；TRAAK：TWIK相关的花生四烯酸K +。