2003 Fiscal Year Final Research Report Summary
Regulation of Mitochondrial Function in Cardiac Myocytes : Kinetics of the Opening of mPTP and it's Physiological Roles
| Project/Area Number |
13670703
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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 | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
KATOH Hideki HAMAMATSU UNIVERSITY, SCHOOL OF MEDICINE, Internal Medicine III, assistant professor, 医学部, 助手 (80314029)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Hidehary HAMAMATSU UNIVERSITY, SCHOOL OF MEDICINE, Internal Medicine III, professor, 医学部, 教授 (50135258)
TERADA Hajime HAMAMATSU UNIVERSITY, SCHOOL OF MEDICINE, Internal Medicine III, assistant professor, 医学部, 講師 (50252177)
SATOH Hiroshi HAMAMATSU UNIVERSITY, SCHOOL OF MEDICINE, Internal Medicine III, assistant professor, 医学部, 助手 (30293632)
HONJO Haruo NAGOYA UNIVERSITY, Environmental Medicine, associate professor, 環境医学研究所, 助教授 (70262912)
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| Project Period (FY) |
2001 – 2003
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| Keywords | mitochondria / confocal microscopy / calcium / diazoxide / permeability transition pore / saponin / cyclosporine A / diazoxide / membrane potential |
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| Research Abstract |
Mitochondrial permeability transition pore (mPTP) has been considered to play important roles not only as a mechanism of ischemia reperfusion injury, but also for the maintenance of cellular function under physiological condition. In this project we aimed to study (1) the kinetics of the opening of mPTP and it's regulation by mitochondrial Ca^<2+> concentration ([Ca^<2+>]m) and mitochondrial membrane potential (ΔΨ_m), (2) the effects of the opening of mPTP on [Ca^<2+>]_m and cytosolic Ca^<2+> concentration ([Ca^<2+>]_c) and (3) the interaction between mitochondria and sarcoplasmic reticulum (SR) by using confocal microscopy.
We have developed methods to monitor [Ca^<2+>]_m and the opening of mPTP in intact and saponin permeabilized cardiac myocytes. By using these methods, we have found that mitochondrial ATP sensitive potassium channel opener, Diazoxide opened mPTP and released Ca^<2+> from mitochondrial matrix to cytosol. This increase in [Ca^<2+>]_c then increased Ca^<2+> transients and Ca^<2+> sparks. Measurement of [Ca^<2+>]_m revealed that Diazoxide reduced [Ca^<2+>]_m. Finally we have investigated the relation between [Ca^<2+>]_m and ΔΨ_m and found that in the pathophysiological condition, where ΔΨ_m was dissipated, opening of mPTP and mitochondrial Na^+/Ca^<2+> exchange were important for the regulation of [Ca^<2+>]_m.
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