Correction of the defective inter-domain interaction of cardiac ryanodine receptor prevents catecholaminergic polymorphic ventricular tachycardia
| Project/Area Number |
21790726
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OKUDA Shinichi Yamaguchi University, 医学部附属病院, 医員 (90530212)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | カテコラミン誘発性心室頻拍 / リアンジン受容体 / 興奮収縮連関 / カルモジュリンキナーゼ / 心室性不整脈 / リアノジン受容体 |
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| Research Abstract |
Catecholaminergic polymorphic ventricular tachycardia(CPVT )is known to be caused by single point mutation taking place in well defined regions of the cardiac ryanodine receptor (RyR2). CPVT mutation causes defective interdomain interaction of RyR2, which reduces the threshold of luminal [Ca2+] for channel activation, sensitizes to the protein kinase A- dependent phosphorylation, and in turn leads to CPVT. In a human CPVT-associated RyR2^<R2474S/+> knock-in (KI) mouse model, CPVT might be able to be prevented by correcting the defective inter-domain interaction of RyR2 and inhibiting Ca2+ leak.
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Report
(3 results)
Research Products
(36 results)
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[Journal Article] Dantrolene, a Therapeutic Agent for Malignant Hyperthermia, Inhibits Catecholaminergic Polymorphic Ventricular Tachycardia in a RyR2(R2474S/+) Knock-In Mouse Model.2010
Author(s)
Kobayashi S, Yano M, Uchinoumi H, Suetomi T, Susa T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Yamamoto T, Matsuzaki M.
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Journal Title
Circ J. 74
Pages: 2579-2584
NAID
Related Report
Peer Reviewed
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[Journal Article] Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction.2010
Author(s)
Xu X, Yano M, Uchinoumi H, Hino A, Suetomi T, Ono M, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Ikeda Y, Ikemoto N, Matsuzaki M.
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Journal Title
Biochem Biophys Res Commun. 394
Pages: 660-666
Related Report
Peer Reviewed
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[Journal Article] Catecholaminergic Polymorphic Ventricular Tachycardia Is Caused by Mutation-Linked Defective Conformational Regulation of the Ryanodine Receptor.2010
Author(s)
Uchinoumi H, Yano M, Suetomi T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, Ikemoto N, Matsuzaki M.
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Journal Title
Cir Res. 106
Pages: 1413-1424
Related Report
Peer Reviewed
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[Journal Article] Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure.2010
Author(s)
Ono M, Yano M, Hino A, Suetomi T, Xu X, Susa T, Uchinoumi H, Tateishi H, Oda 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. 87
Pages: 609-617
Related Report
Peer Reviewed
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[Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor.2009
Author(s)
Kobayashi S, Yano M, Suetomi T, Ono M, Tateishi H, Mochizuki M, Xu X, Uchinoumi H, Okuda S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M.
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Journal Title
J Am Coll Cardiol. 53
Pages: 1993-2005
Related Report
Peer Reviewed
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[Presentation] Increased Affinity of Calmodulin Binding to Cardiac Ryanodine Receptor Corrects the Defective Channel Gating in Failing Hearts2010
Author(s)
Hino A, Yano M, Fukuda M, Suetomi T, Ono M, Xu X, Uchinoumi H, Susa T, Doi M, Okuda S, Kobayashi S, Yamamoto T, Matsuzaki M.
Organizer
Circulation
Place of Presentation
シカゴ アメリカ合衆国
Year and Date
2010-11-23
Related Report
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[Presentation] Correction of Defective Calmodulin Binding to Cardiac Ryanodine Receptor Inhibits Aberrant Ca2+ Release in CPVT-associated Mutation2010
Author(s)
Fukuda M, Yano M, Hino A, Suetomi T, Xu X, Ono M, Uchinoumi H, Doi M, Okuda S, Kobayashi S, Yamamoto T, Matsuzaki M.
Organizer
Circulation
Place of Presentation
シカゴ アメリカ合衆国
Year and Date
2010-11-23
Related Report
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[Presentation] Mutation-linked Defective Domain Interaction within the Ryanodine Receptor Causes Ca2+ Leak Leading to Catecholaminergic Polymorphic Ventricular Tachycardia2010
Author(s)
Suetomi T, Yano M, Fukuda M, Hino A, Ono M, Xu X, Susa T, Uchinoumi H, Oda T, Okuda S, Kobayashi S, Yamamoto T, Ikeda Y, Matsuzaki M.
Organizer
Circulation
Place of Presentation
シカゴ アメリカ合衆国
Year and Date
2010-11-23
Related Report
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[Presentation] Correction of Defective Inter-domain Interaction Within the Cardiac Ryanodine Receptor as a New Therapeutic Strategy Against Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)2009
Author(s)
Uchinoumi H, Yano M, Hino A, Suetomi T, Ono M, Xu X, Oda T, Doi M, Okuda S, Kobayashi S, Yamamoto T, Ikeda Y, Matsuzaki M.
Organizer
Circulation
Place of Presentation
オーランド アメリカ合衆国
Related Report
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[Presentation] Low-dose of β Blocker Improves Cardiac Function in Patients With Acute Heart Failure Partly by Inhibiting Ca2+ Leak Through the Ryanodine Receptor2009
Author(s)
Kobayashi S, Tanaka T, Susa T, Ono M, Uchinoumi H, Okuda S, Doi M, Kawamura S, Yamamoto T, Yano M, Matsuzaki M.
Organizer
Circulation
Place of Presentation
オーランド アメリカ合衆国
Related Report
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[Presentation] Decreased Affinity of Calmodulin to RyR2 May Be a Sauce Mechanism of Leaky Channel in CPVT-associated Mutation2009
Author(s)
Xu X, Yano M, Hino A, Suetomi T, Ono M, Uchinoumi H, Oda T, Doi M, Okuda S, Kobayashi S, Ikeda Y, Yamamoto T, Ohkusa T, Matsuzaki M.
Organizer
Circulation
Place of Presentation
オーランド アメリカ合衆国
Related Report
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[Presentation] Mutation-linked Channel Disorder in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is Caused by Abnormally Tight Domain-Domain Interaction in RyR22009
Author(s)
Suetomi T, Yano M, Hino A, Ono M, Xu X, Susa T, Uchinoumi H, Oda T, Doi M, Okuda S, Kobayashi S, Ikeda Y, Yamamoto T, Matsuzaki M.
Organizer
Circulation
Place of Presentation
オーランド アメリカ合衆国
Related Report
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