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学科主题: 药学
题名:
Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels
作者: Shi, Limin1,2; Bian, Xiling3; Qu, Zhiqiang1,2; Ma, Zegang1,2; Zhou, Yu1,2; Wang, KeWei3; Jiang, Hong1,2; Xie, Junxia1,2
刊名: NATURE COMMUNICATIONS
发表日期: 2013-02-01
DOI: 10.1038/ncomms2439
卷: 4
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: MIDBRAIN DOPAMINERGIC-NEURONS ; PARKINSONS-DISEASE ; SUBSTANTIA-NIGRA ; BASAL GANGLIA ; MOUSE-BRAIN ; POTASSIUM CHANNEL ; KCNQ/M-CURRENTS ; MESSENGER-RNA ; RAT ; EXPRESSION
英文摘要:

The gut-derived orexigenic peptide hormone ghrelin enhances neuronal firing in the substantia nigra pars compacta, where dopaminergic neurons modulate the function of the nigrostriatal system for motor coordination. Here we describe a novel mechanism by which ghrelin enhances firing of nigral dopaminergic neurons by inhibiting voltage-gated potassium Kv7/KCNQ/M-channels through its receptor GHS-R1a and activation of the PLC-PKC pathway. Brain slice recordings of substantia nigra pars compacta neurons reveal that ghrelin inhibits native Kv7/KCNQ/M-currents. This effect is abolished by selective inhibitors of GHS-R1a, PLC and PKC. Transgenic suppression of native Kv7/KCNQ/M-channels in mice or channel blockade with XE991 abolishes ghrelin-induced hyperexcitability. In vivo, intracerebroventricular ghrelin administration causes increased dopamine release and turnover in the striatum. Microinjection of ghrelin or XE991 into substantia nigra pars compacta results in contralateral dystonic posturing, and attenuation of catalepsy elicited by systemic administration of the D2 receptor antagonist haloperidol. Our findings indicate that the ghrelin/KCNQ signalling is likely a common pathway utilized by the nervous system.

语种: 英语
所属项目编号: 2011CB504100 ; 2012CB526703 ; 30930036 ; 81170207 ; 30970919 ; 81000552 ; 31200819 ; 12-1-4-2-(19)-jch
项目资助者: 973 programme ; National Natural Science Foundation of China ; Bureau of Science and Technology of Qingdao
WOS记录号: WOS:000316616400011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50941
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Qingdao Univ, Coll Med, Dept Physiol, Shandong Prov Key Lab Pathogenesis & Prevent Neur, Qingdao 266071, Peoples R China
2.Qingdao Univ, Coll Med, State Key Disciplines Physiol, Qingdao 266071, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Dept Mol & Cellular Pharmacol, Beijing 100191, Peoples R China

Recommended Citation:
Shi, Limin,Bian, Xiling,Qu, Zhiqiang,et al. Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels[J]. NATURE COMMUNICATIONS,2013,4.
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