1996 Fiscal Year Final Research Report Summary
Functional analysis of ryanodine receptor using molecular genetic technique
| Project/Area Number |
08457025
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | University of Tokyo |
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Principal Investigator |
TAKESHIMA Hiroshi University of Tokyo, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70212024)
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| Project Period (FY) |
1996
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| Keywords | ryanodine receptor / intracellular Ca^<2+> / Ca^<2+> release channel / muscle contraction / caffeine |
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| Research Abstract |
The functions of ryanodine receptor subtypes (RyR-1,2 and 3) have been investigated by means of molecular genetic methords, for example generation of knockout moce. Our major findings in this research project are listed below. 1. Generation and characterization of mutant mice lacking RyR-3. Because the physiological role of RyR-3 was totally unknown, we have investigated the role by the generation of mutant mice lacking RyR-3. The results of analysis of the mutant mice showed non-essential function of RyR-3 in muscle cells and lymphocytes. However, the essential function of RyR-3 has been suggested in certain types of neurons. 2. Function of the dihydropyridine receptor (DHPR) in mutant muscle lacking RyR-1. Direct interaction between DHPR and RyR-1 has been proposed to constitute excitation-contraction (e-c) coupling in skeletal muscle cells. We have analyed calcium currents via DHPR in the mutant muscles lacking RyR-1, and have found significant decrease of calcium currents and absence of its facilitation in the mutant cells. The results suport the idea of the direct interaction between DHPR and RyR-1.3. Subtype specificity of ryanodine receptor for e-c coupling in skeletal muscle. We have shown that skeletal muscle contains RyR-1 and RyR-3, and loss of RyR-1 results in e-c uncoupling. Next, RyR-2 cDNA was introduced in the mutant cells. The RyR-2 expression did not restore e-c uncoupling but induced spontaneous calcium ocillasion. The results indicated ability of RyR-1 and inability of RyR-2 and 3 to contribute for calcium signalling in skeletal muscle.
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[Publications] Takeshima, H., Ikemoto, T., Nishi, M., Nishiyama, N., Shimuta, M., Sugitani, Y., Kuno, J., Saito, I., Saito, H., Endo, M., Iino, M.& Noda, T.: "Generation and characterization of mutant mice lacking ryanodine receptor type 3" J.Biol.Chem.271. 19649-19652 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Okuda-Ashitaka, E.Tachibana, S., Houtani, T., Mitami, T., Masu, Y., Nishi, M., Takeshima, H., Sugimoto, T.& Ito, S.: "Identification and characterization of an endogenous ligand for opioid receptor homologue ROR-C" Mol.Brain Res.43. 96-104 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Nishi, M., Houtani, T., Sato, K., Doi, T., Noda, Y., Mamiya, T., Kuno, J., Takeshima, H., Nukada, T., Nabeshima, T., Yamashita, T., Noda, T.& Sugimoto, T.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphaninFQ receptor" EMBO J. (in press).
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「研究成果報告書概要(欧文)」より
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