| Project/Area Number |
11670676
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
OTANI Hideo Kyoto University, Faculty of Medicine, Department of cardiovascular medicine, Instructor, 医学研究科, 助手 (60293867)
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| Co-Investigator(Kenkyū-buntansha) |
HORIE Minoru Kyoto University, Faculty of Medicine, Department of cardiovascular medicine, assistant professor, 医学研究科, 講師 (90183938)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | KATP channel / Myocardial ischemia / Kir 6.1 / SUR / patch clump / phospholipase C / KATPチャネル / 虚血心筋 / Kir6.x / イオンチャネル / K_<ATP>チャネル / ischemic preconditioning |
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| Research Abstract |
In ischemic myocardium decreased intracellular ATP level affects metabolic, electrophysiologic and mechanical performance. One of the most critical protective mechanism for severe myocaraial ischemia is conducted through the activity of the KATP channel. This channel opens when the ATP level drops suppressing inward Ca current, and preserves ATP consumption.
We ligated rat coronary artery to establish the model for myocardial ischemia under various conditions, and found that there is differential expression among the subunits of KATP channel, Kir6.1, Kir6.2 and SUR. This may be one of the protective mechanism in preparation for recurrent ischemia by more easily opens under higher ATP level.
We expressed Kir6.1-Kir6.2 tandem recombinant protein in cultured cells and measured the potassium current to found each chimeric protein had a intermediate channel property between homo-tetramer. We also observed the intracellular distribution and the efficiency of transport of each chymeric channel protein, Kir6.x and SURx, labeled with GFP using confocal microscopy. The variable combination of each isoprotein resulted in remarkable change in the intracellular sorting of the channel protein.
These mechanism may work for subtle control of the activity of KATP channel under various degree of ischemia in the myocardial cells. We also determined the expression and electrophysiological character affected with angiotensin receptor blocker or signal transduction components, such as Na-K ATPase or phospholipase C.
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