Development of novel arrhythmia therapy using K201 binding core in RyR2 molecle
Project/Area Number |
23591082
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Yamaguchi University |
Principal Investigator |
YAMAMOTO Takeshi 山口大学, 医学(系)研究科(研究院), 准教授 (50363122)
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Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Shigeki 山口大学, 医学部附属病院, 講師 (90397993)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | リアノジン受容体 / K201 / E-C coupling / 致死的不整脈 / EC coupling / calmodulin / ryanodine receptor / 興奮収縮連関 |
Research Abstract |
We revealed that S2246L mutation site and K201 binding site are making loop and interacting each other. We further analyze the calmodulin binding to RyR2 and find that K201 binding core signal transmitted to calmoulin binding site, and then transmitted to the channel pore. From these data, we find two new target domains for the arrhythmia treatment.
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Enhanced binding of calmodulin to RyR2 corrects arrhythmogenic channel disorder in CPVT-associated myocytes2014
Author(s)
Fukuda M, Yamamoto T, Nishimura S, Kato T, Murakami W, Hino A, Ono M, Tateishi H, Oda T, Okuda S, Kobayashi S, Koseki N, Kyushiki H, Yano M
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Journal Title
Biochem Biophys Res Commun
Volume: 448(1)
Issue: 1
Pages: 1-7
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Enhanced binding of calmodulin to the ryanodine receptor corrects contractile dysfunction in failing hearts2012
Author(s)
Hino A, Yano M, Kato T, Fukuda M, Suetomi T, Ono M, Murakami W, Susa T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M
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Journal Title
Cardiovasc Res
Volume: 96(3)
Issue: 3
Pages: 433-43
DOI
Related Report
Peer Reviewed
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[Journal Article] Mutation-linked defective interdomain interactions within ryanodine receptor cause aberrant Ca²⁺release leading to catecholaminergic polymorphic ventricular tachycardia2011
Author(s)
Suetomi T, Yano M, Uchinoumi H, Fukuda M, Hino A, Ono M, Xu X, Tateishi H, Okuda S, Doi M, Kobayashi S, Ikeda Y, Yamamoto T, Ikemoto N, Matsuzaki M
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Journal Title
Circulation
Volume: 124(6)
Pages: 682-94
Related Report
Peer Reviewed
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[Journal Article] Mutation-linked defective interdomain interactions within ryanodine receptor cause aberrant Ca2+ release leading to catecholaminergic polymorphic ventricular tachycardia.2011
Author(s)
Suetomi T, Yano M, Uchinoumi H, Fukuda M, Hino A, Ono M, Xu X, Tateishi H, Okuda S, Doi M, Kobayashi S, Ikeda Y, Yamamoto T, Ikemoto N, Matsuzaki M.
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Journal Title
Circulation
Volume: 124
Pages: 682-694
Related Report
Peer Reviewed
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[Presentation] Enhanced Binding of Calmodulin to the Ryanodine Receptor Corrects Abnormal Calcium Handling in Pressure Over Loaded Heart Failure2014
Author(s)
Takayoshi Katoh, Takeshi Yamamoto, Shigehiko Nishimura, Takeki Myoren, Wakako Murakami, Masakazu Fukuda, Makoto Ohno, Hiroki Tateishi, Mamoru Mochizuki, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
Organizer
The 78th Annual scientific Meeting of the Japanese Circulation Society
Place of Presentation
東京国際フォーラム,東京
Year and Date
2014-03-21
Related Report
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[Presentation] Enhanced Binding of Calmodulin to the Ryanodine Receptor Corrects Abnormal Calcium Handling in Pressure Over Loaded Heart Failure2014
Author(s)
Takayoshi Katoh, Takeshi Yamamoto, Shigehiko Nishimura, Takeki Myoren, Wakako Murakami, Masakazu Fukuda, Makoto Ohno, Hiroki Tateishi, Mamoru Mochizuki, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
Organizer
第78回日本循環器学会学術集会
Place of Presentation
東京(東京国際フォーラム)
Related Report
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[Presentation] Dantrolene Inhibits Aberrant Ca2+ Release and Arrhythmogenesis via Enhancing Binding of Calmodulin to RyR2 in CPVT-Associated Mutation2013
Author(s)
Masakazu Fukuda, Takeshi Yamamoto, Shigehiko Nishimura, Takeki Myouren, Takayoshi Katoh, Wakako Murakami, Makoto Ono, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
Organizer
86th Scientific Session of American Heart Association
Place of Presentation
Dallas USA(Oral)
Year and Date
2013-11-16
Related Report
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[Presentation] Dantrolene Inhibits Aberrant Ca2+ Release and Arrhythmogenesis via Enhancing Binding of Calmodulin to RyR2 in CPVT-Associated Mutation2013
Author(s)
Masakazu Fukuda, Takeshi Yamamoto, Shigehiko Nishimura, Takeki Myouren, Takayoshi Katoh, Wakako Murakami, Makoto Ono, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
Organizer
86th Scientific Session of American Heart Association
Place of Presentation
Dallas,Tx, USA
Related Report
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[Presentation] A Novel Selective EP4 Receptor Agonist Improves Intracellular Ca2+ Handling and Cardiomyocyte Function in Intact Failing Cardiomyocytes2013
Author(s)
Wakako Murakami, Shigeki Kobayashi, Takeki Myoren, Shigehiko Nishimura, Takayoshi Katoh, Masakazu Fukuda, Makoto Ono, Hiroki Tateishi, Mamoru Mochizuki, Tetsuro Oda, Shinichi Okuda, Takeshi Yamamoto, Masafumi Yano
Organizer
86th Scientific Session of American Heart Association
Place of Presentation
Dallas,Tx, USA
Related Report
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[Presentation] Enhancement of Calmodulin Binding to RyR2 Inhibits Aberrant Ca2+ Release in CPVT-Associated Mutation2011
Author(s)
Masakazu Fukuda, Masafumi Yano, Takayoshi Kato, Akihiro Hino, Takeshi Suetomi, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Yasuhiro Ikeda, Takeshi Yamamoto, Masunori Matsuzaki
Organizer
American Heart Association Scientific Sessions 2011
Place of Presentation
Florida (USA)
Related Report
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[Presentation] Coupled Conformational Changes in the Local and Global Inter-Domain Interactions Trigger Diastolic Ca2+ Release and Lethal Arrhythmia in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)2011
Author(s)
Takeshi Suetomi, Masafumi Yano, Takayoshi Kato, Masakazu Fukuda, Akihiro Hino, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Yasuhiro Ikeda, Takeshi Yamamoto, Masunori Matsuzaki
Organizer
American Heart Association Scientific Sessions 2011
Place of Presentation
Florida (USA)
Related Report