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IR@PKUHSC  > 北京大学第三临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Pharmacological effects of carvedilol on T-type calcium current in murine HL-1 cells
作者: Deng, Chunyu2; Rao, Fang2; Wu, Shulin2; Kuang, Sujuan2; Liu, Xiaoying2; Zhou, Zhiling2; Shan, Zhixin2; Lin, Quxiong2; Qian, Weimin2; Yang, Min2; Geng, Qingshan2; Zhang, Youyi3; Yu, Xiyong1,2; Lin, Shuguang2
关键词: Carvedilol ; T-type Calcium Current (I(Ca,T)) ; HL-1 cells ; Whole-cell patch-clamp technique
刊名: EUROPEAN JOURNAL OF PHARMACOLOGY
发表日期: 2009-10-25
DOI: 10.1016/j.ejphar.2009.08.032
卷: 621, 期:1-3, 页:19-25
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: CHANNEL BLOCKER ; CA2+ CHANNEL ; VENTRICULAR MYOCYTES ; HEART ; PROLIFERATION ; ANTIOXIDANT ; EXPRESSION ; MIBEFRADIL ; PREVENTS ; DRUG
英文摘要:

Carvedilol is widely used in the treatment of cardiovascular diseases including atrial fibrillation. T-type Ca(2+) channels have been recognized recently in the mechanisms underlying atrial arrhythmias. However, it is unclear whether carvedilol may affect the T-type Ca(2+) channel. The present study evaluated the pharmacological effects of carvedilol on T-type calcium current (I(Ca,T)) in the murine HL-1 cell line. I(Ca,T) was recorded by the whole-cell patch-clamp technique. Calcium transient was monitored by the fluorescent dye Fluo-4/AM and confocal laser scanning microscopy. Carvedilol reversibly inhibited I(Ca,T) in a concentration-dependent manner, with an IC50 of 2.1 mu M. 3 mu M carvedilol was found to decrease the peak I(Ca,T) amplitude at -20 mV from 20.1 +/- 1.8 pA/pF to 10.9 +/- 2.1 pA/pF. Carvedilol significantly shifted the steady-state inactivation curve of I(Ca,T) towards more negative potential by 12.8 mV, while the activation curve was not significantly altered. Carvedilol delayed recovery from inactivation of I(Ca,T), time constant (tau) Was 112.4 +/- 3.5 ms in control and 270.1 +/- 4.7 ms in carvedilol. Carvedilol-induced inhibition rate in I(Ca,T) Was enhanced with the increase in stimuli frequency, the inhibitory rate was 23.2 +/- 4.1% at 0.2 Hz and 47.2 +/- 0.6% at 2 Hz. Carvedilol still produced the significant decrease in the amplitude of I(Ca,T) in the presence of H-89, PKA inhibitor. Carvedilol significantly inhibited the amplitude of the calcium transient in a concentration-dependent manner. These findings indicate that carvedilol inhibits I(Ca,T) in atrial cells by mechanisms involving preferential interaction with the inactivated state of T-type Ca(2+) channel. (C) 2009 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 30672077 ; 30700328 ; 30772620 ; 2006CB503806 ; A2006002
项目资助者: National Natural Science Foundation of China ; National Key Basic Research Program (NKBRP) of China ; Medical Science Foundation of Guangdong
WOS记录号: WOS:000271153000003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52760
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Guangdong Gen Hosp, Guangdong Acad Med Sci, Med Res Ctr, Guangzhou 510080, Guangdong, Peoples R China
2.Guangdong Prov Cardiovasc Inst, Dept Cardiol, Guangzhou 510080, Guangdong, Peoples R China
3.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100083, Peoples R China

Recommended Citation:
Deng, Chunyu,Rao, Fang,Wu, Shulin,et al. Pharmacological effects of carvedilol on T-type calcium current in murine HL-1 cells[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2009,621(1-3):19-25.
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