Stretch-Activated Channels in Vascular Smooth Muslce Cells.

血管平滑肌细胞中的拉伸激活通道。

• 批准号: 09670725
• 负责人: OHYA Yusuke
• 金额: $ 0.9万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670725/
• 关键词: Vascular smooth muscle; Hypertension; SHR; Channel; イオンチャンネル

The arteria] wall is continuously exposed to mechanical stresses such as shear stress and lumial pressure. It is known that mechanical stress caused various biological responses in the arterial wall, However, the machanisms by which signal transduction from mechanical stimuli to intracellular factors occur are not fully understood. We evaluated the stretch-activated (SA) channels in vascular smooth muscle cells by using patch clamp technique. The SA channels were activated by mechanical stress (stretch of the membrane) and allowed Ca^<2+> and Na^+ into the cell. The ion fluxes per se and the following membrane depolarization would cause the cell excitation. The Gd^<3+>, a known specific blocker of SA channels, inhibited SA channels and L-type Ca^<2+> channel with a similar potency in vascular smooth muscle cells. We thus consider that Gd^<3+> is not a specific blocker of SA channels in vascular smooth muscle cells.Electricalan d contractile responses of samll arteries to mechanical stress are reportedly enhanced in spontaneously hypertensive rats (SHR), conpared with WKY rats. We comared SA channels in vascular smooth muscle cells from SHR and WKY.We showed that the activation of SA channels were enhanced in SHR cells.

动脉壁连续地暴露于机械应力，例如剪切应力和管腔压力。已知机械应力引起动脉壁的各种生物学反应，然而，从机械刺激到细胞内因子的信号转导发生的机制尚未完全理解。应用膜片钳技术研究了血管平滑肌细胞牵张激活（SA）通道。SA通道被机械应力（膜的拉伸）激活，并允许Ca^2+和Na^+进入细胞。离子流本身和随后的膜去极化将引起细胞兴奋。Gd^<3+>是已知的SA通道特异性阻断剂，在血管平滑肌细胞中，Gd^<3 +>对SA通道和L型Ca^<2+>通道的抑制效力相似。我们认为Gd^<3+>不是血管平滑肌细胞SA通道的特异性阻断剂，自发性高血压大鼠（SHR）小动脉对机械应力的电收缩反应增强，与WKY大鼠一致。我们比较了SHR和WKY血管平滑肌细胞SA通道的变化，发现SHR细胞SA通道的激活增强。

项目成果

Nakamura Y: "Thiazolidinedione derivatives inhibit calcium channels in vascular smooth muscle from guinea-pig." Br J Pharmacol. 123. 675-682 (1998)

Nakamura Y：“噻唑烷二酮衍生物抑制豚鼠血管平滑肌中的钙通道。”

Ohya Y: "Enhanced electrical activity in mesenteric arteries from salt-loaded Dahl salt-sensitive rats. Action of prostaglandin H_2 on membrane channels." Am J Hypertens. 10. 112S-115S (1997)

Ohya Y：“盐负荷 Dahl 盐敏感大鼠的肠系膜动脉电活动增强。前列腺素 H_2 对膜通道的作用。”

Ohya Y,Adachi N,Setoguchi M,Isao A,Fujishima M.: "Effects of CP-060S on the membrane channels in vascular smooth muscle cells from guinea-pig." Eur J Pharmacol. 330. 93-99 (1997)

Ohya Y、Adachi N、Setoguchi M、Isao A、Fujishima M.：“CP-060S 对豚鼠血管平滑肌细胞膜通道的影响。”

Fujishima S: "Troglitazone increases blood flow in healthy man." Am J Hypertens. 11. 1134-1137 (1998)

Fujishima S：“曲格列酮可增加健康人的血流量。”

Setoguchi M,Ohya Y,Abe I,Fujishima M: "Stretch-activated whole-cell currents in smooth muscle cells from mesenteric resistance artery of guinea-pig." J Physiol (Lond). 501. 343-353 (1997)

Setoguchi M、Ohya Y、Abe I、Fujishima M：“豚鼠肠系膜阻力动脉平滑肌细胞中的拉伸激活全细胞电流。”