内皮细胞电压门控钙离子通道及其功能研究进展
作者:
作者单位:

1)天津大学机械工程学院,天津 300350;2)重庆大学生物工程学院,重庆 400044

作者简介:

Tel: 022-27404934, E-mail: yhcui@tju.edu.cnTel: 86-22-27404934, E-mail: yhcui@tju.edu.cn

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基金项目:

国家自然科学基金(11972252) 和天津市自然科学基金 (17JCYBJC29300) 资助项目。


Research Progress on Voltage-gated Calcium Channels and Their Functions in Endothelial Cells
Author:
Affiliation:

1)School of Mechanical Engineering, Tianjin University, Tianjin 300350, China;2)School of Bioengineering, Chongqing University, Chongqing 400044, China

Fund Project:

This work was supported by grants from The National Natural Science Foundation of China(11972252)and Tianjin Natural Science Foundation (17JCYBJC29300).

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    摘要:

    内皮细胞(endothelial cell,EC)作为不可兴奋细胞,早前通常被认为缺乏功能性电压门控钙离子通道(voltage-gated calcium channel,VGCC),如人脐静脉内皮细胞、牛肺动脉内皮细胞、牛主动脉内皮细胞等。随着膜片钳技术、荧光显微技术、聚合酶链式反应(PCR)技术的发展,越来越多的VGCC在各种内皮细胞中被发现,如人主动脉内皮细胞、大鼠主动脉内皮细胞、大鼠肺微血管内皮细胞等。目前对于VGCC存在与否主要有3种检测方法:利用膜片钳技术对离子通道电流的检测、利用荧光显微技术对胞内钙离子浓度变化的检测、利用PCR技术对离子通道基因或蛋白质表达的检测。内皮细胞不单单是血液和其他相邻组织细胞及基质蛋白间的物理屏障,更重要的是通过细胞膜上VGCC的开放和关闭对细胞和血管组织的生理变化产生显著的影响。一方面,VGCC对胞内钙离子浓度变化的影响,控制着一氧化氮(NO)等血管舒张因子的释放,调节血管张力的平衡。另一方面,作为钙离子内流重要途经的VGCC,经过Ras和MEK通路的诱导、磷酸化PI3K和Akt通路,影响内皮细胞迁移和增殖。此外,部分生理现象,如血管内压力产生的机械应变和血流相关的剪切应力通过激活机械小体,导致通道关闭,引起内皮细胞膜去极化的方式激活VGCC、部分受体、配体的结合及离子通道的开闭需要VGCC的参与,如激活剂为缓激肽的钾离子通道的开闭,激活剂为组胺的阳离子通道的开闭等。总之,鉴于VGCC具有调控内皮细胞兴奋性、分泌、迁移等重要功能,对其深入而广泛的研究对揭示并治疗诸如原发性高血压、动脉粥样硬化等内皮功能性疾病有十分重要的意义。

    Abstract:

    Endothelial cells, as non-excitable cells, were previously thought to lack functional voltage-gated calcium channels (VGCC), such as human umbilical vein endothelial cells, bovine pulmonary artery endothelial cells, bovine aortic endothelial cells, and bovine aorta endothelial cells. With the development of patch clamp technology, fluorescence microscopy technology, and polymerase chain reaction (PCR) technology, more and more VGCC are found in various endothelial cells, such as human aortic endothelial cells, rat aortic endothelial cells, and rat pulmonary microvascular endothelial cells. At present, there are 3 main detection methods for the existence of VGCC: the detection of ion channel current by patch clamp technology, the detection of intracellular calcium ion concentration change by fluorescence microscopy technology, and the detection of ion channel gene or protein expression by PCR. Endothelial cells are not only the physical barrier between blood and other adjacent tissue cells and matrix proteins, but more importantly, exert a significant influence on the physiological changes of cell and vascular tissues through the opening and closing of VGCC on the cell membrane. On the one hand, the effect of VGCC on the change of intracellular calcium ion concentration controls the release of vasodilators such as nitric oxide (NO) and regulates the balance of vascular tone. On the other hand, VGCC, which is an important route for calcium ion inflow, affects endothelial cell migration and proliferation through the induction of a kind of small G protein (Ras) and mitogen-activated proteinkinase kinase (MEK) pathways, the phosphonic acidification of phosphatidylinositol 3 kinase (PI3K) and serine/threonine protein kinase (Akt) pathways. In addition, some physiological phenomena, such as mechanical strain generated by intravascular pressure and shear stress associated with blood flow, activate VGCC by activating mechanical bodies, causing the ATP-sensitive potassium channel () channel to close, causing endothelial cell membranes to depolarize; the binding of some receptors and ligands and the opening and closing of ion channels require the participation of VGCC, such as the opening and closing of potassium ion channels with bradykinin as activator and cation channels with histamine as activator. Hence,in view of the important functions of VGCC in regulating the excitability, secretion and migration of endothelial cells, in-depth and extensive research on VGCC is of great significance for revealing and treating endothelial functional diseases such as essential hypertension and atherosclerosis.

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引用本文

李双君,潘君,崔玉红.内皮细胞电压门控钙离子通道及其功能研究进展[J].生物化学与生物物理进展,2022,49(6):1061-1074

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  • 收稿日期:2021-04-30
  • 最后修改日期:2021-07-22
  • 接受日期:2021-07-26
  • 在线发布日期: 2022-06-21
  • 出版日期: 2022-06-20