MODULATION OF VENULAR MICROVESSEL PERMEABILITY BY CALCIUM INFLUX INTO ENDOTHELIAL-CELLS
MODULATION OF VENULAR MICROVESSEL PERMEABILITY BY CALCIUM INFLUX INTO ENDOTHELIAL-CELLS
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DOI：
10.1096/fasebj.6.7.1563597
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发表时间：
1992-04-01
期刊：
影响因子：
4.8
通讯作者：
CURRY, FE
中科院分区：
文献类型：
--
作者：
CURRY, FE
有人提出，钙离子流入内皮细胞通过钙依赖的收缩过程调节静脉微血管的通透性。最近对通透性内皮细胞单层的研究结果证实了这一假设，即内皮肌动蛋白和肌球蛋白在邻近内皮细胞暴露于炎症因子的收缩过程中存在钙依赖的相互作用。对于暴露于炎症介质后钙流入内皮细胞的途径知之甚少，但有证据表明钙进入途径的性质与调节内皮源性松弛因子（EDRF）释放的钙进入途径相似。刺激EDRF从动脉内皮释放的物质也增加了静脉微血管的通透性。最近发展的方法测量形成单独灌注微血管壁的内皮细胞的细胞质钙浓度，可以直接研究钙流入对静脉微血管通透性的调节。这些实验表明，暴露于增加渗透性的物质（如钙离子载体）后，微血管渗透性的初始增加幅度是由钙离子流入内皮细胞的大小决定的。此外，钙流入内皮细胞的大小受内皮细胞的膜电位调节。内皮细胞膜的去极化减少钙内流并减弱通透性的增加，而内皮细胞膜的超极化则增加钙内流并增强通透性的增加。这些数据符合钙的被动传导通道是钙离子通量的主要途径，导致微血管内皮屏障通透性增加的假设。
It has been proposed that calcium ion influx into endothelial cells modulates the permeability of venular microvessels via a calcium-dependent contractile process. The results of recent investigations using permeabilized endothelial cell monolayers conform to this hypothesis by demonstrating a calcium-dependent interaction of endothelial actin and myosin during the retraction of adjacent endothelial cells exposed to inflammatory agents. Little is known about the pathway for calcium influx into endothelial cells after exposure to mediators of inflammation, but evidence suggests that the properties of the calcium entry pathways are similar to the calcium entry pathways that regulate the release of endothelium-derived relaxing factor (EDRF). Substances that stimulate EDRF release from arterial endothelium also increase venular microvessel permeability. Recently developed methods to measure cytoplasmic calcium concentration in the endothelial cells forming the walls of individually perfused microvessels enable a direct investigation of the modulation of the permeability of venular microvessels by calcium influx. These experiments demonstrate that the magnitude of the initial increase in the permeability of microvessels after exposure to an agent that increases permeability, such as a calcium ionophore, is determined by the magnitude of calcium ion influx into the endothelial cells. Furthermore, the magnitude of the calcium influx into endothelial cells is modulated by the membrane potential of the endothelial cells. Depolarization of the endothelial cell membrane reduces calcium influx and attenuates increases in permeability whereas hyperpolarization of the endothelial membrane increases calcium influx and potentiates increases in permeability. These data conform to the hypothesis that a passive conductance channel for calcium is a major pathway for calcium ion flux responsible to eliciting an increase in the permeability of the endothelial barrier in microvessels.