2006 Fiscal Year Final Research Report Summary
Studies on the developmental and species difference of the cardiac function: return to chick embryonic myocardium and the integration of the study
| Project/Area Number |
17590229
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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 |
General pharmacology
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| Research Institution | Toho University |
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Principal Investigator |
SHIGENOBU Kouki Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50012654)
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| Project Period (FY) |
2005 – 2006
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| Keywords | mouse myocardium / chick embryonic heart / alpha-adrenergic effect / endothelin / Na+, Ca2+-exchanger / T-type Ca2+ channel / K+ channel / species difference |
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| Research Abstract |
1. Mouse myocardium
(1) From the experimental results, it was concluded that Na+, Ca2+-exchanger produces the efflux of Ca2+ and influx of Na+ at the later phase of action potential on the basis of its equilibrium potential, which in turn elicits net inward current, thus contributing the formation of late plateau.
(2) Negative inotropic response of mouse myocardium to the alpha-adrenergic stimulation was mainly due to the augmentation of Na+, Ca2+-exchange. The increase in the sensitivity of contractile protein to Ca2+ is caused by the intracellular alkalization. Specially designed contracture experiments suggested that Ca2+ handling by SR was not modified by alpha-stimulation.
(3) Positive and negative inotropic response to endothelin is caused by the increase in Ca2+ sensitivity of the contractile protein due to the increase in intracellular pH, and increase in the Ca2+ extrusion through the Na+, Ca2+-exchanger, respectively.
2. Chick embryonic myocardium
(1) A selective inhibitor of T-type Ca2+ channel, R(-)-efonidipine showed the negative inotropic effects on the chick embryonic ventricle, suggesting that Ca2+ influx through the T-type Ca2+ channels contributes the contraction of the myocardium at early stages of development.
(2) Calibdotoxin produced the negative inotropic effects on the young embryonic hearts but iberiotoxin did not. Thus, the intermediate conductance K+ channels are present in the early embryonic myocardium, which is characteristic to vascular smooth muscle.
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[Journal Article] Muscarinic receptor subtypes mediating positive and negative inotropy in the developing chick ventricle.2007
Author(s)
Nouchi, H., Kaeriyama, S., Muramatsu, A., Sato, M., Hirose, K., Shimizu, N., Tanaka, H., Shigenobu, K.
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Journal Title
J. Pharmacol. Sci 103
Pages: 75-82
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Involvement of the Na^+/Ca^<2+> exchanger in ouabain-induced inotropy and arrhythmogenesis in guinea-pig myocardium as revealed by SEA0400.2007
Author(s)
Tanaka, H., Shimada, H., Namekata, I., Kawanishi, T., Iida-Tanaka, N., Shigenobu, K
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Journal Title
J. Pharmacol. Sci (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Unique excitation-contraction characteristics of mouse myocardium as revealed by SEA0400, a specific inhibitor of Na+-Ca2+ exchanger.2005
Author(s)
Tanaka, H., Namekata, I., Takeda, K., Kazama, …T., Shigenobu, K.
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Journal Title
Naunyn-Schmiedeberg's Arch. Pharmacol. 371
Pages: 526-534
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Unique excitation-contraction characteristics of mouse myocardium as revealed by SEA0400, a specific inhibitor of Na+-Ca2+ exchanger.2005
Author(s)
Tanaka, H., Namekata, I., Takeda, K., Kazama, A., Shimizu, Y., Moriwaki, R., Hirayama, W., Sato, A., Kawanishi, T., Shigenobu, K.
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Journal Title
Naunyn-Schmiedeberg's Arch., Pharmacol. 371
Pages: 526-534
Description
「研究成果報告書概要(欧文)」より
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