| Project/Area Number |
07457013
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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 physiology
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| Research Institution | Juntendo Universitv School of Medicine |
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Principal Investigator |
OCHI Rikuo Juntendo Univ.Sch.of Med., Proffessor, 医学部, 教授 (10049025)
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| Co-Investigator(Kenkyū-buntansha) |
MASUMIYA Haruko Juntendo Univ.sch.of Med., 医学部, 助手 (30286744)
TATEYAMA Michihiro Juntendo Univ.sch.of Med., 医学部, 助手 (30276472)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Ca^<2+> channel / single channel / gating process / phoisphorylation / isoproterenol / BAY K 8644 / antisence / beta-subunit / Ca培玩薬 / Caアゴニスト |
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| Research Abstract |
The major aim of the present study was to clarify the changes of the gating process of the cardiac L-type Ca^<2+> channels produced by channel phoisphorylation based on single channel analysis. During the course of the study, new problem of the involvement of Ca^<2+> channel beta-subunit on the phosphorylation-dependent modulation arised.
Results
1.Isoproterenolincreased mainly availability (Ps) and slightly openprobability (Po) of the L-type channel to increase the channel current. The increase of its concentration between 1 nM and 0.1 mM did not increase the rate of mode-2 sweeps.
2.The rate of mode-2 sweeps in the presence of BAY K 8644 was significantly increased by isoproterenol.
3.The time course of inactivation of macroscopic Ba^<2+> current was enhanced by nitrendipine and this was enhanced by isoproterenol.
4.Treatment by beta-subunit antisence of cultured adult rabbit ventricular myocytes decreased the L-type current density by 30%, increased the time course of rise and decay of the current by a factor of two and significantly decreased the efficacy of isoproterenol to increase the current.
Future prospect
Accumulating knowledges from molecular biology study using heterologous expression system indicated the multisubuinit organization of L-type Ca^<2+> channels, phosphorylation sites in alpha-1 subunit and phosphorylation of beta subunit. Using antisence technology towards native cardiac myocytes and applying single channel recording technique we have a good chance to disclose the role of beta subunit in Ca^<2+> channel regulation.
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