Activation of galanin receptor 1 inhibits locus coeruleus neurons via GIRK channels
Activation of galanin receptor 1 inhibits locus coeruleus neurons via GIRK channels
复制标题
甘丙肽受体 1 的激活通过 GIRK 通道抑制蓝斑神经元。
DOI：
10.1016/j.bbrc.2018.05.181
复制
发表时间：
2018-09-03
影响因子：
3.1
通讯作者：
Xu, Zhi-Qing David
中科院分区：
文献类型：
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作者：
Bai, Yun-Fei;Ma, Hai-Tao;Xu, Zhi-Qing David
蓝斑（LC）的去甲肾上腺素能神经元与多种脑功能和精神疾病（如成瘾和抑郁）有关。神经肽甘丙肽（GAL）可抑制LC神经元兴奋性，但其机制尚不清楚。在本研究中，我们研究了GAL抑制LC神经元的离子和信号转导机制，采用全细胞膜片钳记录在大鼠脑片上。浴应用GAL减少自发放电，并诱导剂量依赖性超极化的LC神经元，这种效果被减弱敲低Galr 1，但不是Galr 2，证实主要是GALR 1介导的GAL的抑制作用。GAL的抑制作用也分别被百日咳毒素（PTX）、GTP-γ-s或GDP-β-s阻断，表明PTX敏感的G（i/o）蛋白的功能是GAL诱导的超极化所必需的。此外，GIRK通道阻断剂（tertiapin-Q或SCH 2 3390 hydrochloride）可减弱GAL的反应，而BK/SK/K-ATP通道阻断剂或ASK-1/3通道阻断剂对GAL的反应无明显影响，提示GIRK通道在GAL诱导的LC神经元超极化中起重要作用。总之，GAL对LC神经元的抑制作用是由GALR 1通过PTX敏感的G（i/o）蛋白介导的，所述G（i/o）蛋白激活GIRK通道。(C)2018由Elsevier Inc.出版
The noradrenergic neurons of the locus coeruleus (LC) are associated with various brain functions and psychiatric disorders, such as addiction and depression. It has been shown that neuropeptide galanin (GAL) inhibits neuronal excitability in LC, but the mechanisms remain unclear. In the present study, we investigated the ionic and signal transduction mechanisms underlying inhibitory effect of GAL on LC neurons using whole-cell patch clamp recording in rat brain slices. Bath application of GAL decreased the spontaneous firings and induced a dose-dependent hyperpolarization of LC neurons and this effect was attenuated by knockdown of Galr1, but not Galr2, confirming that mainly GALR1 mediates the inhibition effect of GAL. The inhibitory effect of GAL was also blocked by treatments of pertussis toxin (PTX), GTP-gamma-s or GDP-beta-s, respectively, indicating that the functions of PTX sensitive G(i/o) protein are required for GAL-induced hyperpolarization. Moreover, the blockers of GIRK (tertiapin-Q or SCH2 3390 hydrochloride) attenuated the GAL response while blocker of BK/SK/K-ATP channels or TASK-1/3 channels did not affect it significantly, suggesting that GIRK channels play an important role in GAL-induced hyperpolarization in LC neurons. Taken together, the inhibitory effect of GAL on LC neurons is mediated by GALR1 via PTX-sensitive G(i/o) proteins, which activate GIRK channels. (C) 2018 Published by Elsevier Inc.