1994 Fiscal Year Final Research Report Summary
Mechanisms of antiarrhythmic drugs via gene expression
| Project/Area Number |
05670604
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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 | Nagoya University |
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Principal Investigator |
KAMIYA Kaichiro Res.Inst.of Environ.Med., Nagoya Univ., Assistant Professor, 環境医学研究所, 助手 (50194973)
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| Co-Investigator(Kenkyū-buntansha) |
TOYAMA Junji Res.Inst.of Environ.Med., Nagoya Univ., Professor, 環境医学研究所, 教授 (20023658)
KODAMA Itsuo Res.Inst.of Environ.Med., Nagoya Univ., Professor, 環境医学研究所, 教授 (30124720)
KANBE Fukushi Res.Inst.of Environ.Med., Nagoya Univ., Assistant Professor, 環境医学研究所, 助手 (00211871)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Amiodarone / ion channels / action potential / Kv1.5 channels / mRNA |
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| Research Abstract |
In the present study, we examined chronic effects of amiodarone(AM) on action potentials and ionic currents of rabbit and rat ventricular myocytes and Kv1.5, a Shaker-like delayd rectifier K^+ channel. In single ventricular myocytes of rabbits treated with amiodarone 100 mg/Kg/day for 4 weeks, action potential duration (APD) was prolonged. Chronic amiodarone demonstrated decreased in current densities of ICa, IK and Ito. Northern blot analysis showed that levels of Kv1.5 mRNA were decreases in amiodarone treated rat myocytes compared with non treated myocytes. These results suggest that 1)acute and chronic amiodarone exerts divergent effects on action potential configuration and ionic currents in cardiac muscle. 2)prolongation in APD by the long-term treatment of amiodarone was derived from the inhibition of Ito and IK,while shortening of APD by the perfusion of the drug was caused by the inhibition of inward currents, 3)antiarrhythmic action of chronic treatment of amiodarone may be derived by the depression of repolarizing potassium channels through modulation of potassium channels gene expression.
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