Study on ion channel remodeling in atrial fibrillation

心房颤动离子通道重塑的研究

• 批准号: 13670775
• 负责人: YAMASHITA Takeshi
• 金额: $ 1.54万
• 依托单位: The Cardiovascular Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670775/
• 关键词: atrial fibrillation; ion channel; gene expression; remodeling; 不整脈; Kv1.5; 概日リズム; アルコール

To investigate the molecular mechanisms underlying the initiation and maintenance of atrial fibrillation, we analyzed the gene expression of ion channels expressed in the rat atrium including Na^+ channel, Ca^<2+> channel, voltage-dependent K^+ channels, inwardly-rectifying K^+channels, and HCN channels. Various factors known to cause feasibility of atrial fibrillation induction modified the ion channel expression in various ways. Rapid atrial pacing caused immediate upregulation of Kv1.5 and simultaneous downregulation of Kv4.2, Kv4.3, HCN4, and auxiliary subunit of L-type Ca2^+ channel. The gene expression of Kv1.5 and Kv4.2 showed a characteristic circadian variation reverse to each other. Cortisol induced upregulation of Kv1.5 and Kir 2.2. Alcohol caused a different type of ion channel remodeling: upregulation of Kv1.5 and HCN4. These results indicated that various factors surrounding atrial fibrillation caused various types of ion channel remodeling, necessitating the concept of targeting the channel according to the characteristics of the patients.

为了研究心房颤动发生和维持的分子机制，我们分析了大鼠心房中表达的离子通道的基因表达，包括Na^+通道、Ca^<2+>通道、电压依赖性K^+通道、内向整流K^+通道和HCN通道。已知导致房颤诱导可行性的各种因素以各种方式改变了离子通道表达。快速心房起搏可立即上调Kv1.5，同时下调Kv4.2、Kv4.3、HCN 4和L型钙通道辅助亚基。Kv1.5和Kv4.2的基因表达表现出特征性的昼夜变化，彼此相反。皮质醇诱导Kv1.5和Kir 2.2的上调。酒精引起不同类型的离子通道重塑：上调Kv1.5和HCN 4。这些结果表明，心房颤动周围的各种因素引起了各种类型的离子通道重塑，需要根据患者的特点靶向通道的概念。

项目成果

Yamashita T: "Circadian Variation of Cardiac K^+ Channel Gene Expression."Circulation. 107. 1917-1922 (2003)

Yamashita T：“心脏 K^ 通道基因表达的昼夜节律变化。”循环。

山下武志: "心房細動に伴うイオンチャネルリモデリング"心電図. 22. 559-564 (2002)

Takeshi Yamashita：“与心房颤动相关的离子通道重塑”心电图 22. 559-564 (2002)。

籏野誠二, 山下武志: "心房細動に伴う心房筋リモデリング"内科. 89. 28-32 (2002)

Seiji Kasono、Takeshi Yamashita：“与心房颤动相关的心房肌肉重塑”内科医学。 89. 28-32 (2002)

籏野誠二, 山下武志: "心房細動と電気的リモデリング"分子血管病. 3. 65-72 (2002)

Seiji Kasono、Takeshi Yamashita：“心房颤动和电重构”分子血管疾病。3. 65-72 (2002)

山下武志: "医学のあゆみ別冊:循環器疾患 state of arts"医師薬出版. 841 (2001)

Takeshi Yamashita：“医学史特刊：循环系统疾病的艺术现状”石药出版社 841 (2001)。