Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain
文献类型：期刊论文
| 作者 | Wu, Hui-Jun; Wu, Wei; Sun, Hai-Ying; Qin, Guo-Wei5; Wang, Hong-Bing3; Wang, Panwen4; Yalamanchili, Hari Krishna4; Wang, Junwen4; Tse, Hung-Fat; Lau, Chu-Pak |
| 刊名 | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
 |
| 出版日期 | 2011-12 |
| 卷号 | 51期号:6页码:966-973 |
| 关键词 | Acacetin hKv1.5 Tonic blockade Open channel blockade Rate-dependent blockade |
| ISSN号 | 0022-2828 |
| DOI | 10.1016/j.yjmcc.2011.08.022 |
| 文献子类 | Article |
| 英文摘要 | We have demonstrated that the natural flavone acacetin selectively inhibits ultra-rapid delayed rectifier potassium current (I-Kur) in human atria. However, molecular determinants of this ion channel blocker are unknown. The present study was designed to investigate the molecular determinants underlying the ability of acacetin to block hKv1.5 channels (coding I-Kur) in human atrial myocytes using the whole-cell patch voltage-clamp technique to record membrane current in HEK 293 cells stably expressing the hKv1.5 gene or transiently expressing mutant hKv1.5 genes generated by site-directed mutagenesis. It was found that acacetin blocked hKv1.5 channels by binding to both closed and open channels. The blockade of hKv1.5 channels by acacetin was use- and frequency-dependent, and the IC50 of acacetin for inhibiting hKv1.5 was 3.5, 3.1, 2.9, 2.1, and 1.7 mu M, respectively, at 0.2, 0.5, 1, 3, and 4 Hz. The mutagenesis study showed that the hKv1.5 mutants V505A, I508A, and V512A in the S6-segment remarkably reduced the channel blocking properties by acacetin (IC50, 29.5 mu M for V505A, 19.1 mu M for I508A, and 6.9 mu M for V512A). These results demonstrate the novel information that acacetin mainly blocks open hKv1.5 channels by binding to their S6 domain. The use- and rate-dependent blocking of hKv1.5 by acacetin is beneficial for anti-atrial fibrillation. (C) 2011 Elsevier Ltd. All rights reserved. |
| WOS关键词 | HUMAN ATRIAL MYOCYTES ; RECTIFIER K+ CURRENT ; POTASSIUM CHANNEL ; MOLECULAR-BASIS ; KV1.5 CHANNELS ; FIBRILLATION ; VOLTAGE ; DETERMINANTS ; DRUGS ; HEART |
| 资助项目 | Sun Cheh Yeh Heart Foundation of Hong Kong[00000000] ; Innovation and Technology Commission of the Hong Kong SAR Government[ITS/339/09] ; University of Hong Kong[00000000] |
| WOS研究方向 | Cardiovascular System & Cardiology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000296943800012 |
| 出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278322]  |
| 专题 | 天然药物化学研究室 |
| 通讯作者 | Qin, Guo-Wei |
| 作者单位 | 1.Univ Hong Kong, Li Ka Shing Fac Med, Dept Physiol, Pokfulam, Hong Kong, Peoples R China 2.Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Pokfulam, Hong Kong, Peoples R China; 3.Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China; 4.Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Pokfulam, Hong Kong, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wu, Hui-Jun,Wu, Wei,Sun, Hai-Ying,et al. Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2011,51(6):966-973. |
| APA | Wu, Hui-Jun.,Wu, Wei.,Sun, Hai-Ying.,Qin, Guo-Wei.,Wang, Hong-Bing.,...&Li, Gui-Rong.(2011).Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,51(6),966-973. |
| MLA | Wu, Hui-Jun,et al."Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 51.6(2011):966-973. |
入库方式： OAI收割
来源：上海药物研究所
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