通过丸激素对心脏再极化电流的非转录调节
Chang-Xi Bai1, Junko Kurokawa, Masaji Tamagawa
1Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Tokyo 101-0062, Japan.
Circulation
|September 15, 2005
概括
素通过增强电流和抑制电流来缩短心脏动作潜力的持续时间,可能会影响男性的QTc间隔. 这种效应涉及氧化信号和非转录调节.
科学领域:
- 心血管生理学心血管生理学
- 分子心脏病学分子心脏病学
- 内分泌学 在内分泌学.
背景情况:
- 女性表现出比男性更长的QTc间隔和更高的心律失常风险.
- 丸激素与腹腔再极化中与性别相关的差异有关.
- 有限的数据存在于丸激素对心脏离子电流的影响.
研究的目的:
- 为了研究丸激素对心脏肌细胞的电生理学影响.
- 阐明的作用背后的离子机制.
- 探索参与的作用的信号通路.
主要方法:
- 在孤立的几内亚猪心室肌细胞中,补丁电生理学.
- 评估作用电位持续时间 (APD) 和膜电流.
- 药理上抑制特定的离子通道和信号通路.
- 蛋白质酸化的免疫块分析.
主要成果:
- 在生理度下,丸激素迅速缩短了APD.
- APD缩短的结果是IKs增强和I(Ca,L) 抑制.
- 氧化 (NO) 通过NOS3.3调解了的作用.
- 激素通过受体,c-Src,PI3K和Akt通路诱导了Akt和NOS3的酸化.
结论:
- 非转录性调节IKs和I(Ca,L).
- 这代表了控制心脏再极化的一种新机制.
- 的作用可能有助于雄激素在QTc间隔调节中的作用.
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