Calcineurin-independent inhibition of the delayed rectifier K+ current by the immunosuppressant FK506 in rat hippocampal neurons
文献类型：期刊论文
| 作者 | Yu, Yong; Chen, Xue-Qin; Cui, Yao-Yuan; Hu, Guo-Yuan |
| 刊名 | BRAIN RESEARCH
 |
| 出版日期 | 2007-05-07 |
| 卷号 | 1148页码:62-68 |
| 关键词 | calcineurin cyclosporin A delayed rectifier K+ channel fast transient K+ channel FK506 hippocampus immunosuppressant drug rapamycin |
| ISSN号 | 0006-8993 |
| DOI | 10.1016/j.brainres.2007.02.022 |
| 文献子类 | Article |
| 英文摘要 | The immunosuppressant drug FK506 was found to be a potent neuroprotective agent in animal models of brain ischemia. However, the mechanisms underlying the action remain to be elucidated. The delayed rectifier K+ channel has been implicated in ischemic injury and neuronal death in the brain. The aim of the present study is to investigate whether the neuroprotective action of FK506 results from blocking the K+ channel. in acutely dissociated CA1 pyramidal neurons of rat hippocampus, superfusion of FK506 (0.01-100 mu M) selectively inhibited the delayed rectifier K+ current (I-K) with an IC50 value of 13.2 +/- 4.9 mu M. The inhibition of I-K by FK506 (10 mu M) had a rapid onset, and then gradually reached a steady-state level. The inhibition was voltage-dependent, became more potent when the currents were elicited by strong depolarization. Moreover, FK506 (10 mu M) caused marked negative shifts of the steady-state activation and inactivation curves of I-K, and accelerated its recovery from inactivation. Intracellular dialysis of FK506 (30 PM) was ineffective. The inhibition of I-K by FK506 (10 mu M) persisted under the low-Ca2+ conditions that blocked the basal activity of protein phosphatase 2B (calcineurin). Rapamycin did not antagonize FK506 but mimicked it. Cyclosporin A inhibited I-K only at 30 and 100 mu M. Taken together, the results suggest that FK506 exert a direct inhibition on the delayed rectifier K+ channel without involvement of calcineurin. (c) 2007 Elsevier B.V. All rights reserved. |
| WOS关键词 | TRANSIENT FOREBRAIN ISCHEMIA ; OUTWARD POTASSIUM CURRENT ; PYRAMIDAL NEURONS ; CHANNEL ACTIVITY ; ION CHANNELS ; CA1 ; IMMUNOPHILINS ; PHOSPHATASES ; ENHANCEMENT ; STROKE |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000246651800007 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273258]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Cui, Yao-Yuan |
| 作者单位 | 1.Fudan Univ, Dept Neurosurg, Zhongshan Hosp, Shanghai 200032, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Yong,Chen, Xue-Qin,Cui, Yao-Yuan,et al. Calcineurin-independent inhibition of the delayed rectifier K+ current by the immunosuppressant FK506 in rat hippocampal neurons[J]. BRAIN RESEARCH,2007,1148:62-68. |
| APA | Yu, Yong,Chen, Xue-Qin,Cui, Yao-Yuan,&Hu, Guo-Yuan.(2007).Calcineurin-independent inhibition of the delayed rectifier K+ current by the immunosuppressant FK506 in rat hippocampal neurons.BRAIN RESEARCH,1148,62-68. |
| MLA | Yu, Yong,et al."Calcineurin-independent inhibition of the delayed rectifier K+ current by the immunosuppressant FK506 in rat hippocampal neurons".BRAIN RESEARCH 1148(2007):62-68. |
入库方式： OAI收割
来源：上海药物研究所
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