Identification of target ion channels in various model of atrial fibrillation

各种心房颤动模型中目标离子通道的识别

• 批准号: 15590784
• 负责人: YAMASHITA Takeshi
• 金额: $ 0.26万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590784/
• 关键词: atrial fibrillation; ion channel; circadian rhythm; stress; pulmonary vein

1)Spontaneous hypertensive ratAfter recognizing that atrial fibrillation was easily induced in SHR rats, we have found that not ion channels but tissue fibrosis played a major role in the arrhythmogensis. In this model, the gene expression of inward and outward ion channels were preserved similarly to the control WKY rats.2)Ion channels in the pulmonary veinsWe have screened the gene expression of various ion channels and identified that one of pacemaker channels, HCN4, was abundantly expressed. In addition, the cardiomyocytes expressing HCN4 were compartmentalized along with aging, possibly leading to abnormal automaticity.3)Stress-induced atrial fibrillationWe have created a new AF model induced by steroid hormone, where Kv1.5 was remarkably upregulated. Kv1.5 gene expression induced by steroid lead to progressive shortening of refractory period that underlies the arrhythmogenesis.

1)自发性高血压大鼠在认识到自发性高血压大鼠易诱发心房颤动后，我们发现，在心房颤动的发生中起主要作用的不是离子通道，而是组织纤维化。2）肺静脉离子通道我们筛选了多种离子通道的基因表达，并确定了起搏通道之一HCN 4的高表达。另外，随着年龄的增长，表达HCN 4的心肌细胞沿着区室化，可能导致异常的自律性。3）应激诱导的心房颤动我们建立了一种新的类固醇激素诱导的AF模型，其中Kv 1.5显著上调。类固醇诱导Kv1.5基因表达导致不应期进行性缩短，这是卵巢癌发生的基础。

项目成果

Cibenzoline Attenuates Upregulation of Kv1.5 Channel Gene Expression by Experimental Paroxysmal Atrial Fibrillation

西苯唑啉减弱实验性阵发性心房颤动对 Kv1.5 通道基因表达的上调

• 发表时间: 2005
• 期刊: International Heart Journal 46
• 作者: Yamashita Takeshi;Yamashita T;Yamashita Takeshi
• 通讯作者: Yamashita Takeshi

Yamashita T, Sekiguchi A, Iwasaki Y, Sagara K, Iinuma H, Hatano S, Fu L-T, Watanabe H.: "Circadian variation of cardiac K+ channel gene expression"Circulation. 107. 1917-1922 (2003)

Yamashita T、Sekiguchi A、Iwasaki Y、Sagara K、Iinuma H、Hatano S、Fu L-T、Watanabe H.：“心脏 K 通道基因表达的昼夜节律变化”循环。

Relation between variability of ventricular response intervals and exercise capacity in patients with non-valvular atrial fibrillation

非瓣膜性房颤患者心室反应间期变异性与运动能力的关系

• 发表时间: 2004
• 期刊: Circulation Journal 68
• 作者: Yamashita Takeshi;Yamashita T;Yamashita Takeshi;Matsumoto Miwa
• 通讯作者: Matsumoto Miwa

Circadian variation of cardiac K+ channel gene expression

• DOI: 10.1161/01.cir.0000058752.79734.f0
• 发表时间: 2003-04-15
• 期刊: CIRCULATION
• 影响因子: 37.8
• 作者: Yamashita, T;Sekiguchi, A;Watanabe, H
• 通讯作者: Watanabe, H

Progressive nature of paroxysmal atrial fibrillation - Observations from a 14-year follow-up study

• DOI: 10.1253/circj.68.568
• 发表时间: 2004-06-01
• 期刊: CIRCULATION JOURNAL
• 影响因子: 3.3
• 作者: Kato, T;Yamashita, T;Fu, LT
• 通讯作者: Fu, LT