| Project/Area Number |
15390078
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Chiba University |
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Principal Investigator |
NAKAYA Haruaki Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (60113594)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Toshiaki Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (60244159)
OGURA Takehiko Chiba University, Graduate School of Medicine, research associate, 大学院・医学研究院, 助手 (00292673)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥9,800,000 (Direct Cost: ¥9,800,000)
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| Keywords | ATP-sensitive K^+ channel / Heart / Kir6.1 / Transgenic mouse / Ischemia / Action potential / Mitochondria / Kir6.2 / 心筋細胞 / 膜ATP感受性K^+チャネル / 虚血再灌流 / ノックアウトマウス / トランスジェニックマウス |
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| Research Abstract |
It is acknowledged that cardiac ATP-sensitive (K_<ATP>) channel is a hetero-octamer comprising the pore-forming subunit Kir6.2 and the regulatory subunit sulfonylurea receptor (SUR2A). Although another pore-forming subunit Kir6.1 reportedly exists in heart cells, the pathophysiological significance of Kir6.1 in the heart remains unclear. This study was undertaken to evaluate the role of cardiac Kir6.1 protein using transgenic mice overexpressing Kir6.1 gene (Kir6.1TG) in the myocardium. Langendorff-perfused hearts of wild-type (WT) and Kir6.1TG mice were subjected to global ischemia (25 min) followed by reperfusion (120 min). Myocardial infarct size, measured by triphenyltetrazolium chloride staining, in Kir6.1TG hearts was smaller and recovery of contractile function of Kir6.1TG hearts was greater compared with WT hearts. In coronary-perfused ventricular muscle preparations of Kir6.1TG mice, the action potential duration (APD) was longer than that of WT preparations in pre-ischemic period, probably due to downregulation of K^+ channels. During ischemia the APD shortening was accelerated in Kir6.1TG preparations. There was no difference in mitochondrial K_<ATP> channel activity, which was indirectly evaluated by diazoxide-induced flavoprotein oxidation, between Kir6.1TG and WT cardiomyocytes. These findings suggest that Kir6.1 protein in cardiomyocytes affords cardioprotection against ischemia/reperfusion injury.
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