钾通道Kv7.4的选择性调节对中缝背核5-羟色胺能神经元的兴奋性有显著影响。

Selective Modulation of K Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons.

作者信息

Zhao Chen, Su Min, Wang Yingzi, Li Xinmeng, Zhang Yongxue, Du Xiaona, Zhang Hailin

机构信息

Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China.

出版信息

Front Cell Neurosci. 2017 Dec 14;11:405. doi: 10.3389/fncel.2017.00405. eCollection 2017.

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K channel modulators.

起源于中缝背核（DRN）的血清素（5-羟色胺，5-HT）系统与各种情绪和情感相关障碍有关，如焦虑、恐惧和应激。DRN 5-HT神经元的异常活动是这些障碍发生发展的关键因素。在此，我们描述了Kv7.4钾通道在调节DRN 5-HT神经元兴奋性方面的关键作用。我们证明Kv7.4在DRN的5-HT神经元中选择性表达。使用选择性Kv7.4开放剂法舒地尔和Kv7.4基因敲除小鼠，我们证明Kv7.4是DRN 5-HT神经元兴奋性的有效调节剂。此外，我们证明细胞氧化还原信号机制参与了5-HT对Kv7.4的激活。当前研究提示了一种使用钾通道调节剂治疗与DRN 5-HT神经元活动改变相关精神障碍的新策略。