| Project/Area Number |
16590673
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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 | Nagoya University |
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Principal Investigator |
HONJO Haruo Nagoya University, Research Institute of Environmental Medicine, Associate Professor, 環境医学研究所, 助教授 (70262912)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIYA Kaichiro Nagoya University, Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (50194973)
KODAMA Itsuo Nagoya University, Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (30124720)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Atrial fibrillation / Pulmonary vein / Ion channels / Stretch / Electrophysiology / 不整脈基質 / リエントリー / triggered activity / 自動能 / 光学マッピング |
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| Research Abstract |
Spontaneous electrical activities originating from the pulmonary vein myocardial sleeves play important roles in the initiation and maintenance of atrial fibrillation, but little is known about the ionic mechanisms of arrhytmogenic activities in the pulmonary veins. We investigated ion channel expression in rabbit and rat pulmonary veins and compared those in the sinoatiral node and atrial muscle. Hyperpolarization-activated channels (HCN1, HCN4) and Cav1.3 L-type Ca channel mRNAs were abundantly expressed in the sinoatrial node but their expression in the pulmonary veins was less than in the atrial muscle. Inward rectifier K channels (Kir2.1, Kir2.2), cardiac type Na channel (Nav1.5) and Ca-handling proteins (ryanodine receptor and SERCA) mRNAs were lower in the pulmonary veins than in atrial muscle. These results suggest that the unique ion channel expression profile in the pulmonary veins may underlie arrhythmogenic substrates such as impaired conduction and intracellular Ca overload.
Atrial fibrillation is often associated with atrial dilatation. We investigated the effects of stretch-activated channel (SAC) blockers on the vulnerability of atrial fibrillation in intra-atrial pressure-overloaded rabbit hearts. Ga^<3+> reduced the stretch-induced vulnerability. Synthesized peptides, which are reported to block a subset of SAC, and Cl^-channel blockers have no significant effects on atrial fibrillation propensity during pressure overload. Blockade of SAC might be a novel antiarrhythmic approach to atrial fibrillation under conditions of increased atrial pressure.
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