| Project/Area Number |
06670127
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
TAKEYA Kazumi Aichi Medical University, Pharmacology, Professor, 医学部, 教授 (30065528)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Michiko Aichi Medical University, Pharmacology, Research Associate, 医学部, 助手 (10257701)
ANDO Hiroaki Aichi Medical University, Pharmacology, Assistant Professor, 医学部, 講師 (40148317)
HOTTA Yoshihiro Aichi Medical University, Pharmacology, Associate Professor, 医学部, 助教授 (40109757)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Heart / Mitochondoria / Proton / Ca^<2+> / Na^+ / K^+ / Myocardial stretch / High energy phosphates / カルシウム イオン / 高エネルギー燐酸化合物 / 虚血 / 自由エネルギー / Ca^<2+> / H^+ / Na^+ / NMR |
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| Research Abstract |
Cardiac mitochondria are recognized to play an essential role in pumping action of the heart. Mitochondria (about 30 % volume) and heart muscle cells are in intimate co-operative relation of symbiosis from which basic functions of myocardium would be maintained via energy production/utilization and ions transport mechanisms. Recent studies on mitochondria with molecular biologic and NMR techniques provided many informations to understand a possible role for contributing cardiac function maintenance, however, no sufficient data are available for understanding some paradoxical phenomena in ischemic/reperfusion injuries. We, therefore, studied using NMR and ion-fluorometry techniques measuring energy currency related substances of ATP,PCr, Pi and various ions of H^+, Ca^<2+>, Na^+ and K^+ in mitochondria. In 1995, we found that in acute pump failure the change in free energy (-DELTA G : calculated from [ATP]/[ADP][Pi]) predisposed the contractility of the heart in ischemic state. Besides,
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considering into the transport of high energy in ATP via PCr shuttle, and Ca^<2+> mobilization into mitochondria, the contractility of myocardium can be more accurately understandable. In addition, biological contents of Starlings law was analyzed with results indicating the elevation of free Ca^<2+> and Pi with a slight reduction of ATP and PCr. In 1996, we found beneficial effects of inhibitors such as EIPA and omeprasol on H^+ -Na^+ and H^+ -K^+ exchangers on ischemic/reperfusion injuries of the heart. The isolated mitochondria immobilized on the polylysin-coated cover glass on the microscope were superfused with various solution and got information about the ion transport mechanism in mitochondrial membranes : Intramitochondrial pH was elevated by Na^+ and K^+ containing superfusates indicating the existence of antiport mechanisms between proton and these monovalent cations. These transport mechanisms were further confirmed by the inhibitors. Matrix Ca^<2+> in preloaded mitochondria with abnormally high Ca were elevated by reperfusion of either with physiologica concentration of Ca^<2+> or acidified perfusate of pH 6.5. This finding will interprete the "Ca-paradox" at mitochondria level. Further study will be required to get more information and also remedies for mitochondria-involved diseases or pathologic conditions. Less
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