| Project/Area Number |
03454132
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Saga Medical School |
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Principal Investigator |
EHARA Tsuguhisa Saga Medical School Prof., 医学部, 教授 (50037446)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Hiroshi Saga Medical School Lect., 医学部, 講師 (60238962)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | Cardiac muscle / Chloride current / Chloride channel / Cyclic AMP / Muscarinic receptor / ATP / Purine receptor / チャネルキネチックス / 燐酸化 / 心筋 / プリンレセプタ- |
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| Research Abstract |
1. Study of whole cell c1^- current (guinea-pig ventricular and atrial cells). (1) beta-adrenergic and muscarinic regulation of C1^- current (I_<Cl>). Acetylcholine (ACh) depressed the I_<Cl> induced by beta-adrenergic stimulation. ACh also suppressed the I_<Cl> induced by forskolin, but failed to interfere with the one induced by internal application of cyclic AMP. ACH appears to inhibit the beta-receptor-dependent I_<Cl> by deactivating adenylate cyclase through inhibitory G protein. (2) Activation of I_<Cl> by purinergic stimulation. Extracellular application of ATP at muM levels was found to activate a time-independent current very similar to the beta-receptor-dependent I_<Cl>. The relationship between the reversal potential of this current and [Cl]_0 indicated that this current is also a Cl^- current. ADP, AMP, and adenosine were also effective in inducing the I_<Cl>, showing no clear order of potency for the purinoceptor subtypes involved.
2. Study of single C1^- channel (guinea-pig ventricular cells). Cell-attached patch clamp was performed to record single Cl^- channel cur-rents, while the cells were dialyzed with cyclic AMP-containing internal solution through a second pipette. The activity of C1^- channel appeared in some patches during the cell dialysis. Analysis of the open probability (P_0) of the channels, with regard to the P_0 value at their appearance and any changes in P_0 during cell dialysis, suggested that cyclic AMP system make the 'latent' C1^- channels available without influencing their own kinetic behaviour. The channel Seemed to have at least one open state and two closed states; the open time histograms showed one exponential component with a time constant of about 1 s, while the closed time histograms showed two exponential components with time constants of about 0.2 and 1 s. These time constants showed no clear voltage-dependence.
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