Studies on the role of Ttype calcium channels in the cardiovascular system using a specific inhibitor
| Project/Area Number |
18590243
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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 |
TANAKA Hikaru Toho University, Faculty of Pharmaceutical Sciences, Professor (40236617)
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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 |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | T-type calcium channel / dihvelrnnvricline / heart rate / action notential / sinoatrial node / エホニジピン / 心収縮力 / 幼若期 / 心臓 / 自動能 |
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| Research Abstract |
The T-type calcium channel has different properties and distribution for those of the L-type. It is considered to be involved in various physiological and pathophysiological phenomena such as cardiac automaticity, secretion of various active substances, and is therefore anticipated to be a novel therapeutic target. In the this project, I studied the physiological role of the T-type calcium channel using R (-) -efonidipine, the specific inhibitor I found in my previous studies. Contractile force experiments with isolated murine ventricular tissue revealed that the T-type calcium channel contributes to myocardial contraction in the fetal period but not at adulthood. Activation of the T-type calcium channel was involved in the endothelin- 1-induced positive inotropy. Microelectrode recordings in isolated sinoatrial-node preparations revealed that the T-type calcium channel is involved in the pacemaker depolarization of the mouse and guinea-pig but not in the rabbit, which agreed with earliler data on current density. This indicated that the different contribution of the T-type calcium current to pacemaking underlies species difference in heart rate. As it was shown that the factors which determines heart rate is different among species and the condition of the heart, extension of the present study to hearts from various pathological models may lead to the development of novel pharmacological therapy through regulation of heart rate.
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Report
(3 results)
Research Products
(54 results)
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[Journal Article] Species difference in the contribution of T-type calcium current to cardiac pacemaking as revealed by R(-)-efonidipine2008
Author(s)
Tanaka, H., Komikado, C., Namekata, I., Nakamura, H., Suzuki, M., Tsuneoka, Y., Shigenobu, K., Takahara, A
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Journal Title
J. Pharmacol. Sci 107
Pages: 99-102
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Membrane-labelled MDCK cells and confocal microscopy for the analyses of cellular volume and morphology2008
Author(s)
Iida-Tanaka, N., Namekata, I., Tamura, M., Kawamata, Y., Kawanishi, T., Tanaka, H
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Journal Title
Biol. Pharmaceut. Bull 34
Pages: 731-734
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Intracellular mechanisms and receptor types for endothelin- 1-induced positive and negative inotropy in mouse ventricular myocardium.2008
Author(s)
Namekata, I., Fujiki, S., Kawakami, Y., Moriwaki, R., Takeda, K., Kawanishi, T., Takahara, A., Shigenobu, K., Tanaka, H
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Journal Title
Naunyn Schmied Arch. Pharmacol 376
Pages: 386-395
Description
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[Journal Article] (R)-ACX, a pancreatic b-cell selective sulfonylurea, does not aggravate myocardial ischemia-reperfusion damage2007
Author(s)
Namekata, I., Yamaguchi, Y., Moriguchi, S., Yamazaki, S., Terasawa, A., Yamagishi, R., Aikawa, T., Saito, T., Kurashima, K., Seri, K., Imamura, Y., Akita, H., Shigenobu, K., Tanaka. H
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Journal Title
Eur. J. Pharmacol 577
Pages: 211-218
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Involvement of intracellular Ca^<2+> in the regulatory volume decrease after hyposmotic swelling in MDCK cells2007
Author(s)
Iida-Tanaka, N., Namekata, I., Kaneko, M., Tamura, M., Kawanishi, T., Nakamura, R., Shigenobu, K., Tanaka, H
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Journal Title
J. Pharmacol. Sci 104
Pages: 397-401
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Analysis of arrhythmogenic profile in a canine model of chronic atrioventricular block by comparing in vitro effects of the class III antiarrhythmic drug nifekalant on the ventricular action potential indices between normal heart and atrioventricular block heart2007
Author(s)
Takahara, A., Nakamura, H., Nouchi, H., Tamura, T., Tanaka, T., Shimada, H., Tamura, M., Tsuruoka, N., Takeda, K., Tanaka, H., Shigenobu, K., Hashimoto, K., Sugiyama, A
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Journal Title
J. Pharmacol. Sci 103
Pages: 181-188
NAID
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^+ exchanger in ouabaininduced inotropy and arrhythmogenesis in guinea-pig myocardium as revealed by SEAO4002007
Author(s)
Tanaka, H., Shimada, H., Namekata, I., Kawanishi, T., lida-Tanaka, N., Shigenobu, K
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Journal Title
J. Pharmacol. Sci 103
Pages: 241-246
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhancement of methoxamine-induced contractile responses of rat ventricle in streptozotocin-induced diabetes is associated with αlAadrenoceptor upregulation2006
Author(s)
Kamata, K., Satoh, T., Matsumoto, T., Noguchi, E., Taguchi, K., Kobayashi, T., Tanaka, H., Shigenobu, K
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Journal Title
Acta. Physiol. Scand 188
Pages: 173-183
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Blockade by NIP-142 of carbachol-induced action potential shortening and GIRK 1/4 channel2006
Author(s)
Matsuda, T., Ito, M., Ishimaru, S., Tsuruoka, N., Saito, T., Iida-Tanaka, N., Hashimoto, N., Yamashita, T., Tsuruzoe, N., Tanaka, H., Shigenobu, K
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Journal Title
J. Pharmacol. Sci 101
Pages: 303-310
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effect of R(-)-efonidipine, a selective T-type Ca^<2+> channel blocker, on myocardial automaticity2006
Author(s)
Komikado, C., Shimada, H., Takeda, K., Namekata, I., Kawanishi, T., Tanaka, H., Shigenobu, K
Organizer
The 23rd Annual Meeting of ISHR Japanese Section
Place of Presentation
Chiba
Description
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