Cellular Pharmacology of Hyperpolarization-Relaxation Coupling

超极化弛豫耦合的细胞药理学

• 批准号: 07457020
• 负责人: YANAGISAWA Teruyuki
• 金额: $ 4.74万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457020/
• 关键词: K^+ channels; Hyperpolarization; Relaxation; K^+ channel openers; K^+ channel blockers; intracellular CaX^<2+> concentration; Coronary artery; Cerbral artery; レボクロマカリム; ベラパミル; カリウムチャネル開口薬(オープナ-)

The involvement of large conductance Ca^<2+>-activated K^+ channels (BK) and ATP-sensitive K^+ (K_<ATP>) channels in regulation of arterial tone was examined by measuring the change in intracellular Ca^<2+> concentration ([Ca^<2+>]_i) simultaneously with force of contraction in the canine or porcine coronary or basilar arterial smooth muscles. At resting condition, levcromakalim reduced [Ca^<2+>]_i and tone. Levcromakalim suppressed the serotonin-induced increases in [Ca^<2+>]_i and contraction, the maximum effects of which were much greater than those of nicardipine. The inhibitory effects of levcromakalim were blocked by glibenclamide but not by tetraethylammonium or iberiotoxin. Levcromakalim may reduce the Ca^<2+>-sensitivity of the contractile proteins. Thus, levcromakalim can be a candidate of therapeutic agents for delayd vasospasm after subarachnoid hemorrhage, since in the canine basilar artery levcromakalim reduces [Ca^<2+>]_i and vascular tone independently of the states of … More BK channels.The elucidation of the inhibitory of the hyperpolarization induced by K^+ chnnel openers on the Ca^<2+> movements and force of contraction produced by either the stimulation with agonists or depolarization with high KCI has shown as following : When the plasma membrane is hyperpolarized by K^+ channel openers, voltage-dependent L-type Ca^<2+> channels are deactivated and the influx of Ca^<2+> is decreased. The hyperpolarization of the plasma membrane also has another inhibitory effects on the membrane-associated enzyme activity, phospholipase C.The IP_3 production and IP_3-induced Ca^<2+> release from intracellular stores related with the stimulation of the agonist receptors are inhibited by the hyperpolarization of the plasma membrane by K^+ channel openers. The voltage-dependence of the Ca^<2+> sensitivity of contractile elements. Furthermore, membrane hyperpolarization induced by various K^+ channel openers, relaxd canine coronary arteries more profoundly than decreased [Ca^<2+>]_i.Thus, the membrane voltage may regulate intracellular enzyme activities, including contractile elements. This new facet of signal transduction therefore should be considered in the control of vascular tone. Less

通过<ATP>测定犬或猪冠状动脉或基底动脉平滑肌收缩力时细胞内Ca^&lt;2 +&gt;浓度（[Ca^&lt;2+]_i）的变化，研究了大电导Ca^&lt;2+&gt;激活的K^+通道（BK）和ATP敏感的K^+（K_）通道在动脉张力调节中的作用。在静息状态下，左克罗卡林降低[Ca^&lt;2+&gt;]_i和张力。左克罗卡林抑制降钙素引起的[Ca^&lt;2+&gt;] i升高和收缩，其最大效应远大于尼卡地平。格列本脲可阻断左克罗卡林的抑制作用，但四乙铵或伊比利亚毒素不能阻断左克罗卡林的抑制作用。左克罗卡林可降低收缩蛋白的Ca^2+敏感性。因此，左克罗卡林可以作为治疗蛛网膜下腔出血后迟发性血管痉挛的候选药物，因为在犬基底动脉中，左克罗卡林降低[Ca^&lt;2+&gt;]_i和血管紧张度，而不依赖于 ...更多信息 钾通道开放剂引起的超极化对激动剂刺激或高KCl去极化引起的Ca^2+运动和收缩力的抑制作用已阐明如下：当质膜被K^+通道开放剂超极化时，电压依赖性L型Ca^2+通道失活，Ca^2+内流减少。质膜的超极化对膜相关酶磷脂酶C的活性也有抑制作用。K^+通道开放剂引起的质膜超极化可抑制与激动剂受体激动有关的IP_3产生和IP_3诱导的胞内Ca^2+释放。收缩性成分的Ca^2+敏感性的电压依赖性。此外，各种K^+通道开放剂引起的膜超极化对犬冠状动脉的舒张作用比降低[Ca^&lt;2+&gt;]_i更显著，因此，膜电压可能调节细胞内酶的活性，包括收缩因子。因此，在控制血管张力时应考虑信号转导的这一新方面。少

项目成果

柳澤 輝行・須貝 和幸: "K^+チャネルと血管平滑筋." 脳神経外科速報,6(8) 585-589,1996.6・8. 585-589 (1996)

Teruyuki Yanagisawa 和 Kazuyuki Sugai：“K^+ 通道和血管平滑肌。”，6(8) 585-589，1996.6/8 (1996)。

Yuji, OKADA,Teruyki, YANAGISAWA & Norio, TAIRA: "Membrane potential regulates the Ca^<2+> sensitivity of contractile elements in coronary arterial smooth muscle" Heart Vessels. (Suppl.9). 150-152 (1995)

雄二、冈田、照之、柳泽

Sugai K, Yanagisawa T, etal.: "Levcromakalim decreases aytopalasmic Ca^<2+>,vascular tone and Ca^<2+> sensitivity in canine basilar artery" Fund.Clim.Pharmacol. in press. (1998)

Sugai K、Yanagisawa T 等人：“Levcromakalim 降低犬基底动脉中的细胞浆细胞 Ca^<2>、血管张力和 Ca^<2> 敏感性”Fund.Clim.Pharmacol。

Toshio, YAMAGISHI,Teruyuki, YANAGISAWA,Keisuke, SATHO & Norio, TAIRA: "Relaxant mechanisms of cyclic AMP-increasing agents in porcine coronary artery" Europ.J.Pharmacol.251 (2/3). 253-262 (1994)

山岸敏夫、柳泽辉之、佐藤启介

柳澤 輝行: "新薬理学入門" 南山堂, 372 (1997)

Teruyuki Yanagisawa：“新药理学导论”Nanzando，372（1997）