The role of plasmalemmal Ca^<2+> channels and intracellular Ca^<2+> stores in vascular smooth muscles during the development of vascular resistance

血管平滑肌质膜Ca^2通道和细胞内Ca^2储存在血管阻力发展过程中的作用

• 批准号: 04660325
• 负责人: ITO Katsuaki
• 金额: $ 1.34万
• 依托单位: Miyazaki 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: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04660325/
• 关键词: Resistance vessels; Ca channels; Sarcoplasmic reticulum; Contraction; Intracellular Ca; Contractile protein; Phosphorylation; Membrane potential; 血管平骨筋; ryanodine

In this study, the roles of plasmalemmal Ca^<2+> channels and sarcoplasmic reticulum (SR), intracellular Ca^<2+> stores, in the development of tension in vascular smooth muscle, especially in resistance vessels, were investigated. The major findings are as follws.1) Regulation of cytoplasmic Ca^<2+> ([Ca^<2+>]i) by Ca^<2+> channel and SR.I analyzed the effects of ryanodine and cyclopiazonic acid, modifiers of SR functions, on [Ca^<2+>]i, mesured with fura-2, and the tension of rat mesenteric resistance arteries. The results suggest that SR plays as a buffer to decrease [Ca^<2+>]i at a resting state, while it amplifies a contraction by releasing Ca^<2+> when transmembrane Ca^<2+> influx increased.2) Ca^<2+> entry pathways following activation of alpha1-adrenoceptor. When alpha1-adrenoceptors of resistance vassels was activated by low concentration of agonist, Ca^<2+> influx through voltage-dependent Ca^<2+> channel (VDC) was enhanced without any depolarization. This influx triggered Ca^<2+> release from SR.A high concentration of agonist caused depolarization, which in turn enhanced the Ca^<2+> influx through VDC.Besides this, Ca^<2+> entry through a pathway other than VDC also occurred. This entry was sensitive to K^+ channel blockers but not to dihydropyridine Ca^<2+> channel blockers.3) Functions of ion channels in the hypertensive vessels. In vascular smooth muscles from spontaneously hypertensive rate voltage-dependent Ca^<2+> channels were active at the resting state, which produced an active tension and activated Ca^<2+>-activated K^+ channels. Increased Ca^<2+> influx provided more Ca^<2+> to SR, then increased Ca^<2+> release from SR.

本研究探讨了质膜Ca^2+通道和肌浆网（SR）在血管平滑肌，特别是阻力血管张力形成中的作用。本研究的主要结果如下：1）Ca^<2+>通道和SR对胞浆Ca^<2+>（[Ca^<2+]i）的调节。本研究分析了SR功能调节剂ryanodine和cyclopiazonic acid对Fura-2测定的[Ca^<2+]i和大鼠肠系膜阻力动脉张力的影响。结果表明，在静息状态下，SR可作为一种缓冲剂降低[Ca^<2+>]i，而当跨膜Ca^<2 +>内流增加时，SR可通过释放Ca^<2 +>来放大收缩。当低浓度激动剂激活阻力血管α 1肾上腺素能受体时，电压依赖性Ca ^<2 +>通道（VDC）的Ca^<2 +>内流增强，但无任何去极化。高浓度的激动剂引起去极化，从而增强了钙离子通过VDC的内流，除此之外，还出现了钙离子通过VDC以外的途径内流。这种进入对K^+通道阻断剂敏感，但对二氢吡啶类Ca^<2+>通道阻断剂不敏感。3）高血压血管中离子通道的功能。在自发性高血压大鼠的血管平滑肌中，电压依赖性Ca^2+通道在静息状态下是活跃的，这产生了主动张力并激活了Ca^2+激活的K^+通道。增加Ca^2+内流可使SR中的Ca^2+增加，然后增加SR中的Ca^2+释放。

项目成果

Asano, M., Matsuda, T., Hayakawa, M., Ito, K.M.&Ito, K.: "Increased resting Ca^<2+> maintains the myogenic tone and activated K^+ channels in arteries from young spontaneously hypertensive rats." European Journal of Molecular Pharmacolpgy. 247. 295-304 (1

浅野，M.，松田，T.，早川，M.，伊藤，K.M.

Naganobu,K., Takagi,M., Kawasaki,H. & Ito,K.: "Modification by cyclopiazonic acid and ryanodine of depolarization-induced constriction in rat mesenteric artery" Eur.J.Pharmacol.251. 307-310 (1994)

长信，K.，高木，M.，川崎，H.

永延清和、伊藤勝昭(浦川紀元、唐木英明 編): "平滑筋実験法入門(V.抵抗血管の機械的反応測定法を分担執筆)" 文永堂出版(印刷中), (1994)

长野清和、伊藤胜明（浦川纪元、卡拉木英明编）：《平滑肌实验方法导论（合着V.阻力血管的机械响应测量方法）》文内堂出版社（正在印刷），（1994年）

Naganobu, K., Takagi, M., Kawasaki, H.&Ito, K.: "Modification by cyclopiazonic acid and ryanodine of depolarization-induced constriction in rat mesenteric artery." European Journal of Pharmacology. 251. 307-310 (1994)

长信，K.，高木，M.，川崎，H.

Naganobu, K.&Ito, K.: Methods to measure mechanical response of small arteries. (in Japanese). Introduction to Experiments on Smooth Muscles (ed.Urakawa, N.&Karaki, H.) Bun'eido Syuppan (in press),

长信，K.