| Project/Area Number |
07307025
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 総合 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Yamanashi Medical University |
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Principal Investigator |
HASHIMOTO Keitaro Yamanashi Medical University・Department of Pharmacology Professor, 医学部, 教授 (10004665)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Itsuo Nagoya University・Research Institute of Environmental Medicine Professor, 環境医学研究所, 教授 (30124720)
ENDOH Masao Yamagata University・School of Medicine・Department of Pharmacology Professor, 医学部, 教授 (40004668)
KANNO Morio Hokkaido University・School of Medicine・Department of Pharmacology Professor, 医学部, 教授 (00109422)
NISHI Katsuhide Kumamoto University・School of Medicine・Department of Pharmacology Professor, 医学部, 教授 (00040220)
TAIRA Norio National Institution for Academic Degrees Professor, 学位授与機構, 教授 (60004553)
木村 純子 福島県立医科大学, 医学部, 講師 (10186322)
飯島 俊彦 秋田大学, 医学部, 教授 (30004724)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1995: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | antiarrhythmic drug / ion channel / receptor / Na-H exchange / arrhythmia / electrophysiology / クラスIII抗不整脈薬 / Kチャネル / Caチャネル / Clチャネル / 筋小胞体 / 細胞内pH / Na・Ca交換 / 心収縮力 |
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| Research Abstract |
Electrophysiological mechanisms of generation of lethal arrhythmias are the basis of the pharmacological treatment of the prevention of cardiac sudden deaths. Our group consisted of electropharmacologists interests in cardiac arrhythmias and mechanical failure tried to find solutions to treat lethal arrhythmias using variousmethods. Dr.Nakaya studied effects of amiodarone on the acetylcholine sensitive K channels and Naactivated K channels of isolated cardiac myocytes and showed a role of these channel changes in the action petential prolongation, which is important for amiodarone's effectiveness on lethal ventricular arrhythmias. Dr.Iijima showed potentiating effect of NO on the opening of ATP dependent K channels during ischemic insults. Dr.Kanno examined thiamine derivatives on the delayd rectifier K channels. Dr.Taira expressed cardiac K channels in Xenopus oocytes and showed the usefulness of this method to screen K channel acting drugs. Dr.Kodama showed a role of Cl channels and sarcoplasmic Ca channels in the stretch induced tachycardia, which may also play a role in the ventricular excitability. Dr.Nishi also showed a possible antiarrhythmic effect of Cl channel blockers. Dr.Endoh, Tsujimoto, Kimura and Hashimoto proposed possible antiarrhythmic effects of inhibitors of Na/Ca exchange or Na/H exchage, alpha_1 receptors. In the era of negative clinical results of using Na, K andCa channel blockers to treat sudden cardiac deaths, our results showed possibilities of pharmacological modulations of cardiac channels, receptors and alpha exchagers on treating lethal arrhythmias.
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