| Project/Area Number |
04670105
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | HOKKAIDO UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
KANNO Morio HOKKAIDO UNIVERSITY SCHOOL OF MEDICINE, Professor, 医学部, 教授 (00109422)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | L-Type Cardiac Channel / Cell-attached patch / Phorbolestar / TPA / Endothelim-1 / Protein kinase C / Rabbit / Cardiomyceste / ウサギ心筋細胞 / エンドセリン / Cキナーゼ / ホルボールエステル類 |
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| Research Abstract |
Recordings of single channel activities of cardiac l-type Ca^<2+> channels using a cell-attached patch clamp technique, and subsequent analvses of the recordings were confirmed to be sufficiently applicable to the present study aiming to determine whether cardiac protein kinase C( PKC) participates in regulating cardiac L-type Ca^<2+> channels.
The present study using isolated rabbit ventricular myocytes revealed that 12-0-tetradecanoyl phoorbol-13-acetate(TPA), a direct activator of PRC.did not affect single Ca^<2+> channel activities, the result being consistent with the reported data showing no influence on macroscopic Ca2+ currents which was recorded by means of a whole-cell patch clamp technique. Endothelin-1(ET-1) which is known to activate PKC through PIP_2 hydrolvsis after activation of cardiac ET receptors, was also found not to givesignificant influence on the single Ca^<2+> channel activities.
These facls cleary indicate that activation of cardiac PKC.even if it occurs directly or indirecily through a receptor mechanism. is not rsponsible to instantaneous regulation of L-type Ca^<2+> channels. differing from the cAMP-A kinase system.
However. these findings contradict the fact that ET-1 is able to establish a PKC inhibitor(H-7, sta urosporine)-suppressible, nifedipine-sensitive delayd pnase of positive inotropic effect in guiea pig atria.
PKC activation, not instantaneously but through a long range pathway of intracellular signal transducing process, may have a role in regulating 1-type Ca^<2+> channels by either inhibition of dephosphrylation or recruitement of sleeping Ca2+ channels.
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