| Project/Area Number |
63570103
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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 | AICHI MEDICAL UNIVERSITY |
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Principal Investigator |
TAKEYA Kazumi AICHI MEDICAL UNIVERSITY, PHARMACOLOGY, PROFESSOR, 医学部, 教授 (30065528)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Hiroaki AICHI MEDICAL UNIVERSITY, PHARMACOLOGY, ASSISTANT, 医学部, 助手 (40148317)
HOTTA Yoshihiro AICHI MEDICAL UNIVERSITY, PHARMACOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (40109757)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1988: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Intracellular Na / ^<23>Na-NMR / Cardiac glycosides / Working heart / Frequency-force r. / Resting Na fluxes / Ericaceous toxin / Ca-signal / 細胞内Na / 心筋 / Na-NMR / 頻度収縮力関係 / リドカイン / 細胞内Na^+ / 細胞外Na^+ / Fura-2-Caシグナル / アセビ毒 (ATX-III) / β-刺激剤 |
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| Research Abstract |
Intacellular sodium ionic activity(aNa_i) or concentration in the working heart muscle was estimated by either Na^+-sensitive microelectrode(ISME) or ^<23>Na-NMR spectroscopy with object to clarify the role of Na^+ for the development of positive inotropy by cardioactive drugs such as cardiac glycosides, ericacious toxins(GTX-I, ATX-III) and Na channel modulators (lidocaine,- TTX). We established the methods for evaluating Na_i by NMR spectroscopy with and without using shift reagent of Dy(TTHA)^<3->. Fura-2 Ca-signaal was also measured to know the relation between Na^+_ and Ca^2+_. The positive inotropic mechanisms could be divided from the view point of ionic fluxes at sarcoplasmic membrane into two groups: the one is primarily dependent on the Na influx increment and the other is produced by the primary increase in calcium influx via calcium channel. The Na-dependent and calcium-dependent positive inotropy was distinguished by a simple methods of recording "rested state contraction"; Sodium-dependent PIE was characterized by the earlier development of peak force of contraction about 100 msec than primarily Ca-dependent PIE. Fura-2 Ca-signal in Na-originated inotropy was characterized by the elevation of resting level of the signal without any change in transient Ca-signal amplitude during a twitch. The frequency-force relationship in guinea-pig papillary muscle was available to know the mechanism of action to determine either Na-dependent or Ca-dependent. The origin of Na contributing the PIE of cardiac glycoside was found to depend not only on Na-influx during action potential but on the resting influx: The PIE of ouabain could be observed in a experimental condition of stopping the voltage dependent Na influx by TTX and partial depolarization. ATX III or GTX I is a useful agent for producing the increment of Na^+ in cardiac cells that was verified by the measurement of ^<23>NMR spectroscopy.
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