Electropharmacological analysis of the signal transduction mechanisms of the delayd rectifier potassium channel of heart cells.
| Project/Area Number |
03454141
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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 |
General pharmacology
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| Research Institution | Akita University |
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Principal Investigator |
IIJIMA Toshihiko Akita University, Pharmacology, Professor, 医学部, 教授 (30004724)
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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 |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Ventricular cells / Patch-clamp method / Adenylate cyclase / Forskolin derivative / Delayd rectifier K^+ current / L-type Ca^<2+> current / Aortic endothelial cell / intracellular Ca^<2+> / 単離心室筋細胞 / 細胞内情報伝達機構 / L型カルシウムイオンチャンネル / 遅延整流カリウムイオンチャンネル / フォルスコリン / 血管内皮細胞 / モルモット心室筋細胞 / 遅延整流カリウムイオンチャンネル電流 / アデニル酸シクラ-ゼ / ベ-タアドレナリン受容体 |
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| Research Abstract |
This study was designed to investigate the differential modulation of the L-type Ca^<2+> (I_<Ca>) and the delayd rectifier K^+ current (I_K) by direct activation of adenylate cyclase in guinea pig ventricular cells. Isoproterenol equally and simultaneously increased both I_<Ca> and I_K in a same threshold concentration, but a water soluble forskolin derivative, NKH477, increased I_K at lower threshold concentrations than that for increasing I_<Ca>. Selective stimulation of beta-1 adrenoceptors, on the other hand, elicited an increase in I_<Ca> more sensitively than I_K. These results suggest that a simple signal transduction pathway from beta adrenoceptors to I_<Ca> and I_K channels mediated through adenylate cyclase and cyclic AMP-dependent protein kinase is not sufficient to explain these differences. It is, therefore, concluded that I_<Ca> and I_K channels could be differentially regulated during beta adrenoceptor stimulation.
Mechanisms responsible for the sustained elevation in intracellular free Ca^<2+> concentration ([Ca^<2+>]_i) in response to histamine and ATP were also studied in cultured human aortic endothelial cells loaded with the fluorescent Ca^<2+> indicator fura-2. Results indicate that the sustained elevation of [Ca^<2+>]_i is resulted from the Cl^--sensitive entry of extracellular Ca^<2+> in human aortic endothelial cells.
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Report
(3 results)
Research Products
(7 results)
