| Project/Area Number |
08670778
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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 |
TERADA Hajime Hamamatsu University School of Medicine, Internal Medicine III,Reseach Associate, 医学部, 助手 (50252177)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Hideharu Hamamatsu University School of Medicine, Photon Medical Research Center, Associa, 遺伝子医学研究センター, 助教授 (50135258)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Na^<2+> / Ca^<2+> exchanger, / Ca^+ overload, / Metabolic inhibition, / Arrhythmia / Na / Ca交換機構 / Ca過負荷 / 不整脈 / 強心配糖体 / 興奮-収縮連関 / 再灌流障害 / 代謝阻害 / acidosis |
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| Research Abstract |
Ca^<2+> influx via reverse-mode Na^+/Ca^<2+> exchanger was responsible for the Na^+ withdrawal Ca^<2+> transient (SWCT), which is caused by low Na^+ perfusion in isolated cardiac myocytes. The SWCT was inhibited during metabolic inhibition despite an increase in [Na^+] while it was increased on the washout of metabolic inhibitor. It was suggested that Na^+/Ca^<2+> exchanger was inhibited during metabolic inhibition in spite of an increase in electrical gradient of Na^+.
KB-R7943, a specific inhibitor of reverse-mode Na^+ /Ca^<2+> exchanger, did not change the cellular contraction and Ca^<2+> transient in steady-state condition. KB-R7943 also did not change the Ca^<2+> content in the sarcoplasmic reticulum, post-rest potentiation of contraction and Ca^<2+> transient, and the action potential. On the other hand, KB-R7943 inhibited an increase in diastolic [Ca2^<2+>]i and spontaneous Ca^<2+> oscillation in myocytes in which [Na^+]i was increased by strophanthidin while it did not inhibit the positive inotropic effect of strophanthidin. In addition, KB-R7943 reduced the incidence of reoxygenation-induced arrhythmias and facilitated the recovery of contraction after reoxygenation. These results suggested that Ca^<2+> influx via reverse-mode Na^+/Ca^<2+> exchanger dose not have the significant roles in normal excitation-contraction coupling and positive inotropy of cardiac glycoside while it is related to arrhythmogenesis and Ca^<2+> overload in myocytes in which [Na^<2+>]i was elevated by cardiac glycoside and metabolic inhibition.
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