| Project/Area Number |
15591636
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | The University of Tokushima |
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Principal Investigator |
OSHITA Shuzo Tokushima University, School of Medicine, Department of Anesthesiology, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (60144945)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIYAMA Yoshinobu Tokushima University, School of Medicine, Department of Anesthesiology, Assistant professor, 大学院・ヘルスバイオサイエンス研究部, 講師 (30243702)
NAKAYA Yutaka Tokushima University, School of Medicine, Department of Nutrition, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (50136222)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Ischemic Preconditioning / Cardioprotection / Patchclamp configuration / Potassium channel / Mitochondria / Vascular smooth muscle cells / Anesthetics / Isoflurane / 心筋保護効果 / Kチャネル |
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| Research Abstract |
Ischemic Preconditioning is a phenomenon in which brief intermittent periods of ischemia are paradoxically protective against subsequent ischemic injury. To characterize the interaction sarcolemmal and mitochondrial ATP-sensitive K channel (KATP) on cardioprotection, we studied pretreatment effects of 2,4-dinitrophenol, a protonophore that uncouples mitochondrial respiration from ATP synthesis, on both flavoprotein oxidation, an index of mitochondrial uncoupling and sarcolemmal KATP activation in isolated rat ventricular myocytes. Effects of 5-hydroxydecanoic acid, a mitochondrial KATP inhibitor, on the pretreatment effects were also studied. Major findings of this study were that pretreatment of mitochondrial uncoupler sensitizes flavoprotein oxidation and sarcolemmal KATP activation. In the presence of 5-hydroxydecanoic acid the sensitizing effects were completely abolished. Without metabolic inhibition, sensitized myocardium represents almost normal flavoprotein oxidation and sarcol
… More
emmal KATP activity. These results suggest that, if we assume a memory molecule, direct effects of the memory molecule potentiates mitochondrial uncoupling and sarcolemmal KATP are negligible, but the memory molecule potentates mitochondrial uncoupling and sarcolemmal KATP in the face of metabolic impairment. In addition, the production of the memory molecule is 5-hydroxydecanoic acid-sensitive.
Next, we evaluated the effects of isoflurane on the K_<ATP> channel activities in cultured rat smooth muscle cells. Openings of K_<ATP> channels were identified on the basis of the characteristic single-channel conductance (28±4pS), activation by 100 μM pinacidil, and block by 3 μM glibenclamide in cell-attached configuration. Application of isoflurane to bath solution during cell-attached recording significantly activated K_<ATP> channels. In contrast to cell-attached patches, isoflurane did not induced activation on K_<ATP> channel currents in outside-out patchclamp configuration. Isoflurane induced activation of K_<ATP> channels was abolished by a combination of PKA inhibitor peptide. Our results indicated that isoflurane activated K_<ATP> channels in rat smooth muscle cells via PKA activation K_<ATP> channel currents Less
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