Electropharmacology and molecular biology of the human cardiac K channels
| Project/Area Number |
09670761
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
HAGIWARA Nobuhisa Tokyo Women's Medical University Cardiology, Instructor, 医学部, 講師 (00180802)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Human myocardium / K channels Ca channels / Patch clamp method / Antiarrhythmic drugs / 抗不整脈薬 / 抗不整脈表 |
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| Research Abstract |
The duration of the cardiac action potential is governed by the balance mainly between inward Na+, Ca2+ currents and outward K+ currents that flow during the depolarization phase of the action potential. Depolarization of human atrial cells activates a transient outward current (Ito), leaving a sustained outward current after continued depolarization. Depolarization-induced sustained outward current could be distinguished from Ito by differences in 4-aminopyridine (4AP) sensitivity and its voltage dependency. The sustained outward current is highly sensitive to 4AP with IC50 value of less than 100uM and it showed rapid activation and did not inactivate during long depolarization. Thus, this sustained outward current resembled the characteristics similar to the Kv 1.5 channel current.
The inward Ca2+ current showed electrophysiological similarity to those reported in other cardiac myocytes. In the human myocardium, the effect of beta-adrenergic agonists on ICa has been well established. However, a relatively small number of studies have been made of the effect of phosphodiesterase (PDE) inhibitors on ICa. In our studies, the regulation of Ca2+ current by phosphodiesterase (PDE) inhibitor was different between human and other cardiac species. Selective PDE III inhibitors of pimobendan and its primary metabolite UD-CG 212 significantly increased ICa in a dose dependent manner (EC5O=1.1 uM, Emax=249% for pimobendan, EC5O=1.8 uM, EC5O=174% for UD-CG 212). These values were significantly greater than in other cardiac species. Thus, these seems to be a considerable species differences in the distribution of the PDE III isozyme.
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Report
(3 results)
Research Products
(18 results)
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[Publications] T.Yajima., H,Nagashima., R,Tsutsumi-Sakai., N,Hagiwara., S,Hosoda., T,Quertermous., H,Kasanuki., M,Kawana.: "Functional activity of the CFTR Cl^- channel in human myocardium." Heart and Vessels.12. 255-261 (1998)
Description
「研究成果報告書概要(欧文)」より
Related Report
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