| Project/Area Number |
10044266
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Nagoya University |
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Principal Investigator |
KODAMA Itsuo Nagoya Univ., Res Inst. of Environ. Med., Professor, 環境医学研究所, 教授 (30124720)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGISHI Yoshiko Nagoya Univ., Res Inst. of Environ. Med., Research Associate, 環境医学研究所, 助手 (50024659)
HONJO Haruo Nagoya Univ., Res Inst. of Environ. Med., Associate Professor, 環境医学研究所, 助教授 (70262912)
BOYETT Mark リーズ大学, 生理学, 教授
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | sinoatrial node / ion channel / action potential / gap junction / pacemaker activity / electrophysiology / immunohistochemistry / simulation / 筋小胞体 / 迷走神経 |
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| Research Abstract |
1. Regional differences and morphological and functional heterogeneity of pacemaker cells were investigated in the rabbit sinoatrial (SA) node, and mathematical models were developed.
2. Action potential duration was greatest at the center of the SA node and declined to the crista terminalis. Analysis of membrane current and effects of channel-specific blockers revealed that this may be result of smaller density of the rapid delayed rectifier K+ current and the 4-aminopyridine-sensitive sustained current in the center.
3. There was a sharply demarcated boundary between connexin43-expressing atrial myocytes in the crista terminalis and connexin 45/connexin40-expressing SA node cells, but on the endocardial side, a transitional zone was detected where connexin43 and connexin45 expression merged.
4. Block of CaィイD12+ィエD1 release from sarcoplasmic reticlum by ryanodine shifted the leading pacemaker site from the SA node center toward the septum. In the periphery, ryanodine suppressed diastoli
… More
c depolarization often resulting in irregular excitation, whereas in the center, ryanodine caused no substantial changes in action potentials. These results suggest that CaィイD12+ィエD1 release from sarcoplasmic reticlum may play more important roles in the periphery than in the center.
5. Electrical stimulation of postganglionic vagal nerves caused a transient pacemaker shift toward the periphery close to the superior or inferior vena cava. This may reflect regional differences in the responsiveness of SA node cells to acetylcholine.
6. Mathematical models of action potentials in the periphery and center of the SA node were developed based on membrane current data. Simulated action potentials were consistent with those recorded experimentally and model behaviors in response to block of various ion channels were also qualitatively the same as those observed experimentally. In the one dimensional model, incorporating regional heterogeneity, spontaneous excitation initiated in the center and propagated to the periphery. Those models serve useful tools to study the physiological significance of heterogeneity and regional differences of SA node pacemaker cells. Less
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