Studies of membrane-associated enzyme activities which are regulated by membrane potential

受膜电位调节的膜相关酶活性的研究

基本信息

批准号：
05670082
负责人：
YANAGISAWA Teruyuki
金额：
$ 1.34万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670082/
关键词：
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

项目摘要

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.

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.因此，存在一些可能的转导机制，通过改变生理盐溶液（PSS）的KCL浓度（PSS）或KCOS来影响膜电位水平的变化，或者通过kcl-抑制或菲堡酯刺激的肌肉的敏感性影响CA^<2+>敏感性。在灌注中，灌注90 mm kc1-2.5 mm cac.5 mm cacl_2 psacl_5 mm cacl_2cca（90） 5 mM Kcl-2.5 mM CACL_2-PSS（5K-2.5CA）或去除外胞外Ca^<2+>（[Ca^<2+>] _ 0），并添加1 mM EGTA（90K-0CA）诱导的降低[Ca^<2+>] _ I和leasaseation。由90K-0CA诱导的松弛速度慢于5K-2.5CA诱导的降低，而[Ca^<2+>] i的降低没有显着差异。 [Na^+] _ 0的降低并没有减慢0CA中的放松。 30K-0CA中的[Ca^<2+>] I-Force关系曲线是在5K-0CA中，在90K-0CA中。 Levcromakalim的效果被glibenclmide阻塞，并通过20 mm -kc1 pSs. [Ca^<2+>] I-Force关系曲线通过更改[K^+] _ 0在2.5 mm Cacl_2-PSS中逐步进行[K^+] _ 0逐步获得的[CAC+] _ 0，通过更改[CACL_2-PSS在2.5 mm CACL_2-PSS中的右图，而通过[CA^<2 <2>] _ / k 0 in clage in clagniation Flognation。 KCO诱导的超极化降低了收缩元件的CA^<2+>灵敏度。肌膜虫有信号转导系统调节收缩元件的Ca^<2+>敏感性，包括通过膜电位水平与酶活性的敏感性。