Institute of Physiology, University of Würzburg, Würzburg, Germany.
Neuropharmacology. 2011 Oct-Nov;61(5-6):918-23. doi: 10.1016/j.neuropharm.2011.06.020. Epub 2011 Jul 1.
Two-pore-domain K(+) (K(2)P) channels are highly expressed in neurons and cardiac myocytes. In this study we investigated the potency of the antidepressant fluoxetine to inhibit brain and cardiac K(2)P channels, TREK-1, TASK-1 and THIK-1. Maximal sensitivity was detected for TREK-1, which was inhibited by 77% when expressed in HEK-293 cells and Xenopus oocytes. Alternative translation initiation (ATI) generates two different protein products from a single transcript of TREK-1. Electrophysiological analysis of two polypeptides engineered by mutagenesis (TREK-1[M53I], TREK-1[ΔN52]) revealed reduced current amplitude and K(+) selectivity of the truncated TREK-1 isoform. The sensitivity of TREK-1[ΔN52] to fluoxetine decreased by 70%, indicating that the first 52 amino acids are essential for TREK-1 sensitivity to this drug.
双孔域钾(K+) (K2P) 通道在神经元和心肌细胞中高度表达。在这项研究中，我们研究了抗抑郁药氟西汀抑制脑和心脏 K2P 通道（TREK-1、TASK-1 和 THIK-1）的效力。TREK-1 的最大敏感性被检测到，当在 HEK-293 细胞和非洲爪蟾卵母细胞中表达时，其抑制率为 77%。TREK-1 的选择性剪接（ATI）从单个 TREK-1 转录本产生两种不同的蛋白质产物。通过突变工程构建的两种多肽（TREK-1[M53I]、TREK-1[ΔN52]）的电生理分析表明，截断的 TREK-1 同工型的电流幅度和 K+选择性降低。TREK-1[ΔN52]对氟西汀的敏感性降低了 70%，表明第一个 52 个氨基酸对于 TREK-1 对这种药物的敏感性是必需的。
