2003 Fiscal Year Final Research Report Summary
Molecular mechanism underlying the modulation and regulation of voltage-dependent L-type Ca^<2+>+ channel gating.
Project/Area Number |
13672274
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | The University of Tokyo |
Principal Investigator |
AKAHANE Satomi The University of Tokyo, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学系研究科, 助手 (00184185)
|
Project Period (FY) |
2001 – 2003
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Keywords | calcium channel / calcium / calcium antagonist / dihyrdropyridines |
Research Abstract |
The voltage-dependent L-type Ca^<2+> channel plays a key role in the spatial and temporal regulation of Ca^<2+>. In cardiac excitation-contraction coupling, Ca2 tinduced Ca^<2+> release (CICR) from ryanodine receptors (RyRs), triggered by Ca^<2+> entry through the nearby L-type Ca^<2+> channel, induces the Ca^<2+>-dependent inactivation (CDI) of the Ca2ア channel. We demonstrated that the CICR-dependent CDI of L-type Ca^<2+> channels, under control of the privileged cross-signaling between L-type Ca^<2+> channels and RyRs, plays important roles for monitoring and tuning the SR Ca^<2+> content via changes of AP waveform and the amount of Ca^<2+>-influx during AP in ventricular myocytes.
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[Publications] Bernard, C., Corzo, G., Adachi-Akahane, S., Foures, G., Kanemaru, K., Furukawa, Y., Nakajima, T., Darbon, H.: "Solution structure of ADO1, a toxin extracted from the saliva of the assassin bug, Agriosphodrus dohrni."PROTEINS : Structure, Function, Bioinformatics. 54. 195-205 (2004)
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[Publications] Izumi-Nakaseko, H., Yamaguchi, S., Ohtsuka, Y., Ebihara, T., Adachi-Akahane, S., Yasushi Okamura: "DHP-insensitive L-type-like Ca channel of ascidian acquires sensitivity to DHP with single amino acid change in domain III P-region."FEBES Letters.
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[Publications] Yamaguchi, S., Zhorov, B.S., Yoshioka K., Nagao, T., Ichijo, H., Adachi-Akahane, S.: "Key roles of Phe^<1112> and Ser^<1115> in the pore-forming IIIS5-S6 linker of L-type Ca^<2+> channel α_<1C> subunit (Ca_v1.2) in binding of dihydropyridines and action of Ca^<2+> channel agonists."Mol.Phamracol.
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「研究成果報告書概要(欧文)」より
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