Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta
文献类型：期刊论文
| 作者 | Wu, Chen2; Yang, Kechun2; Liu, Qiang2; Wakui, Matoko3; Jin, Guo-Zhang1 ; Zhen, Xuechu1; Wu, Jie2
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| 刊名 | NEUROPHARMACOLOGY
 |
| 出版日期 | 2010-12 |
| 卷号 | 59期号:7-8页码:567-572 |
| ISSN号 | 0028-3908 |
| 关键词 | Tetrahydroberberine Dopaminergic neurons Substantia nigra compacta ATP-sensitive K+ channel Rotenone Parch-clamp |
| DOI | 10.1016/j.neuropharm.2010.08.018 |
| 文献子类 | Article |
| 英文摘要 | Tetrahydroberberine (THB) exhibits neuroprotective effects but its targets and underlying mechanisms are largely unknown. Emerging evidence indicates that ATP-sensitive potassium (K-ATP) channels in the substantia nigra pars compacta (SNc) promote Parkinson disease (PD) pathogenesis, thus blocking K-ATP channels may protect neurons against neuronal degeneration. In the present study, we tested a hypothesis that THB blocks K-ATP channels in dopaminergic (DA) neurons acutely dissociated from rat SNc. Using perforated patch-clamp recording in current-clamp mode, the functional K-ATP channels can be opened by persistent perfusion of rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Bath-application of THB reversibly blocks opened K-ATP channels in a concentration-dependent manner, which is comparable to a classical K-ATP channel blocker, Tol. Compared to THB analogs, l-stepholidine (l-SPD) or l-tetrahydropalmatine (l-THP), THB exhibits more profound blockade in K-ATP channels. In addition, exposure of THB alone to the recorded neuron increases action potential firing, and THB also restores rotenone-induced membrane hyperpolarization in the presence of dopamine D2 receptor antagonist (sulpiride), suggesting that THB exhibits an excitatory effect on SNc DA neurons through the block of K-ATP channels. Collectively, the blockade of neuronal K-ATP channels by THB in SNc DA neurons is a novel pharmacological mechanism of THB, which may contribute to its neuroprotective effects in PD. (C) 2010 Elsevier Ltd. All rights reserved. |
| WOS关键词 | CA1 PYRAMIDAL NEURONS ; L-STEPHOLIDINE ; ALPHA-ADRENOCEPTORS ; RECEPTOR SUBTYPES ; BLOOD-PRESSURE ; K+ CHANNELS ; (-)-STEPHOLIDINE ; HIPPOCAMPUS ; AGONISTS ; CURRENTS |
| 资助项目 | 973-project, China[2009CB52200] ; CNSF, China[30825042] |
| WOS研究方向 | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:000284436400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278709]  |
| 专题 | 院士及顾问专家 |
| 通讯作者 | Wu, Jie |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China 2.St Josephs Hosp, Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA; 3.Hirosaki Natl Hosp, Hirosaki, Aomori, Japan; |
| 推荐引用方式 GB/T 7714 | Wu, Chen,Yang, Kechun,Liu, Qiang,et al. Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta[J]. NEUROPHARMACOLOGY,2010,59(7-8):567-572. |
| APA | Wu, Chen.,Yang, Kechun.,Liu, Qiang.,Wakui, Matoko.,Jin, Guo-Zhang.,...&Wu, Jie.(2010).Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta.NEUROPHARMACOLOGY,59(7-8),567-572. |
| MLA | Wu, Chen,et al."Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta".NEUROPHARMACOLOGY 59.7-8(2010):567-572. |
入库方式： OAI收割
来源：上海药物研究所
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