Role of Abnormal Intracellular Calcium Dynamics in the genesis of electrical alternans in the heart
| Project/Area Number |
18590784
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
TANAKA Hideo Kyoto Prefectural University of Medicine, 医学研究科, Assistant Professor (60236619)
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| Co-Investigator(Kenkyū-buntansha) |
OYAMADA Masahito Kyoto Prefectural University of Medicine, 医学研究科, Associate Professor (30183255)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,730,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | cardiomvoc / calcium ion / electrical alternans / arrhythmia / confocal microscopy / sarcoplasmic reticulum / Va-Ca exchange |
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| Research Abstract |
This study was designed to clarify the role of intracellular calcium dynamics in the electrical alternans; a clinically useful indicator for the development of fatal ventricular tachyarrhythmias. By applying a dual-view, rapid scanning confocal microscopy for simultaneous detection of both the intracellular calcium dynamics and the corresponding membrane potentials to Langendorff-perfused rat hearts, we conducted confocal imaging of the fluo4- and RH237-signals at cellular levels. With this novel approach, following results were obtained.
1. We succeeded in detecting both the intracellular calcium dynamics and membrane potentials simultaneously in the perfused rat heart.
2. Under atrio-ventricular conduction block, individual myocytes exhibited calcium waves sporadically with no discernible membrane depolarization.
3. Under low K perfusion with isoproterenol, burst pacing of the heart resulted in genesis of triggered activity and subsequent calcium oscillation mediated by calcium waves that were accompanied by membrane oscillation.
4. Such calcium wave-mediated oscillatory membrane potentials were attenuated by ryanodine and SEA0400, a blocker for Na-Ca exchange.
5. Reduced calcium release from the sarcoplasmic reticulum, by ryanodine failed to evoke calcium alternans. However, high-frequency pacing of the heart at 4-5 Hz resulted in development of calcium alternans, whereas the individual myocytes showed no beat-to-beat alternans of action potential waveforms.
In summary the present results indicate an essential role of calcium waves in the genesis of triggered activity. On the other hands, calcium alternans evoked presumably by depressed calcium release function were not accompanied by electrical alternans, suggesting that electrical alternans is not responsible for the cellular heterogeneity of calcium handings, but regional heterogeneity in the heart.
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Report
(3 results)
Research Products
(42 results)
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[Journal Article] Genaration of reentracnt arrhythmias by dominant-negativeinhibition of connexin43 in neonatal rat cultured myocyte mononlayers2008
Author(s)
Nakagami, T., Tanaka, H., Dai, P., Lin, SF., Tanabe, T., Mani, H., Fujiwara, K., Matsubara, H., Takamatsu, T
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Journal Title
Cardiovasc Res (E-publication on April 24)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Enhanced activity of ventricular Na^+-HCO_3^- cotransport in pressure-overload hypertrophy2007
Author(s)
Yamamoto, T., Shirayama, T., Sakatani, T., Takahashi, T., Tanaka, H., Takamatsu, T., Spitzer, KW., Matsubara, H
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Journal Title
Am J Physiol Heart Circ Physiol 293
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Abnormal calcium dynamics in the cardiomyocytes and Alteration of gap junctional distribution in injured hearts2007
Author(s)
Tanaka, H., Oyamada, M., Tsujii, E., Mani, H., Nakagami, T., Fujiwara, K., Takamatsu, T
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Journal Title
Jpn JElectrocardiol (in Japanese) 27
Pages: 230-236
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Calcium imaging2006
Author(s)
Nakagami, T., Tanaka, H., Takamatsu T
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Journal Title
Handbook of Staining and Bioimaging (Youdosha)
Pages: 237-245
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Nipkow disc scanning2006
Author(s)
Fujiwara, K., Tanaka, H., Takamatsu, T
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Journal Title
Handbook of Staining and Bioimaging (Youdosha)
Pages: 275-279
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of intracellular calcium waves in triggered arrhythmias. - simultaneous confocal recording of single-cell membrane potentials and calcium dynamics in the rat heart-2007
Author(s)
Tanaka, H., Fujiwara, K., Nakagami, T., Mani, H., Oyamada, M., Takamatsu, T
Organizer
ESC Congress, Wien
Place of Presentation
Austria
Year and Date
2007-02-09
Description
「研究成果報告書概要(欧文)」より
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