| Project/Area Number |
05670082
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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 | Tohoku University |
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Principal Investigator |
YANAGISAWA Teruyuki Tohoku University School of Medicine Associate professor, 医学部, 助教授 (90133941)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | hyperpolarization / potassium channel opener / phospholipase C / phorbor ester / protein kinase C / Ca sensitivity / coronary artery / levcromakalim / 蛋白リン酸化酵素C / Ca感受性 / 血管平滑筋 / Kチャンネル開口薬 / 収縮蛋白質 |
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| Research Abstract |
Studies in our laboratory have demonstrated that KCl-induced depolarization potentiates the increased Ca^<2+> sensitivity of contractile elements induced by endothelin-1 and that various K^+ channel openers (KCOs) which hyperpolarize membrane reduce the Ca^<2+> sensitivity and to inhibit agonist-induced contraction and synthesis of IP_3 in porcine or canine coronary artery. Thus, there are some possible transduction mechanisms by which the changes in level of membrane potential by altering KCl concentration in physiological salt solution (PSS) or by KCOs influence the Ca^<2+> sensitivity in high KCl-depolarized or phorbor ester-stimulated muscles.
After the perfusion with 90 mM kc1-2.5 Mm CaCl_2 PSS (90K-2.5Ca), repolarization produced by 5 mM KCl-2.5 mM CaCl_2-PSS(5K-2.5Ca) or the removal of extracellualr Ca^<2+> ([Ca^<2+>]_0) and addition of 1 mM EGTA (90K-0Ca) induced decreases in [Ca^<2+>]_i and relaxation. The relaxation induced by 90K-0Ca was slower than induced by 5K-2.5Ca without significant difference in the decrease in [Ca^<2+>]i. The reduction of [Na^+]_0 did not slow down the relaxation in 0Ca. The [Ca^<2+>]i-force relation curve in 30K-0Ca was been that in 5K-0Ca and that in 90K-0Ca. The effect of levcromakalim was blocked by glibenclmide and counteracted by 20 mM -KC1 PSS.The [Ca^<2+>]i-force relationship curve obtained by changing [K^+]_0 stepwise in 2.5 mM CaCl_2-PSS was located to the right of that by changing [Ca^<2+>]_0 in 90 mM KCl-PSS.Thus, KCl-depolarization increases and hyperpolarization induced by KCOs decreases the Ca^<2+> sensitivity of contractile elements. There are signal transduction systems for sarcolemma to regulate the Ca^<2+> sensitivity of contractile elements including with enzyme activities by the level of membrane potential.
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