| Project/Area Number |
05670635
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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 |
Circulatory organs internal medicine
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| Research Institution | Tokai university school of medicine |
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Principal Investigator |
NAKAZAWA Hiroe Tokai Univ.school of Medicine Dept.of Physiology, professor, 医学部・生理科学, 教授 (20110885)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIMORI Kouji Tokai Univ.school of Medicine, Dept.of Physiology, associate professor, 医学部・生理科学, 講師 (60184636)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | superoxide / nitric oxide / peroxynitrite / myocyte / cytotoxicity / active oxygen / Reperfusion Injury / NADPHオキシダーゼ |
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| Research Abstract |
The effects of peroxynitrite (ONOO^-) on cultured cardiac myocytes were examined by simultaneous measurements of intracellular Ca^<2+> ([Ca^<2+>]i) and contractile function. On exposure to 0.2mM ONOO^-, [Ca^<2+>]i increased to beyond the systolic level within 5 min with a concomitant decrease in spontaneous contraction, followed by complete arrest. Addition of a L-type Ca^<2+> channel blocker or removal of extracellular Ca^<2+> prevented the ONOO^--induced increase in [Ca^<2+>]i ; indicating that the increase in [Ca^<2+>]i was caused by the enhanced influx of Ca^<2+> through the plasma membrane and not by the enhanced release from sarcoplasmic reticulum (SR). Plasma membrane fluidity and concentration of the thiobarbiturate acid-reactive substance (TBARS) in the cells remained unchanged by the ONOO^- treatment. The complete cessation of contraction of myocytes persisted even under the massive increase in [Ca^<2+>]i which was induced by an additional saponin (5muM) treatment. In conclusion, ONOO^- increases [Ca^<2+>]i in myocytes through disturbance of Ca^<2+> transport systems in the plasma membrane and impairs contractile protein.
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