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Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels
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
2013-02-01
DOI10.1038/ncomms2439
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
WOS记录号WOS:000316616400011
项目编号2011CB504100 ; 2012CB526703 ; 30930036 ; 81170207 ; 30970919 ; 81000552 ; 31200819 ; 12-1-4-2-(19)-jch
资助机构973 programme ; National Natural Science Foundation of China ; Bureau of Science and Technology of Qingdao
引用统计
被引频次:38[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50941
专题北京大学药学院
北京大学药学院_分子与细胞药理学系
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
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GB/T 7714
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.
APA Shi, Limin.,Bian, Xiling.,Qu, Zhiqiang.,Ma, Zegang.,Zhou, Yu.,...&Xie, Junxia.(2013).Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels.NATURE COMMUNICATIONS,4.
MLA Shi, Limin,et al."Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels".NATURE COMMUNICATIONS 4(2013).
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