INTRACELLULAR CALCIUM, CURRENTS, AND STIMULUS-RESPONSE COUPLING IN ENDOTHELIAL-CELLS
INTRACELLULAR CALCIUM, CURRENTS, AND STIMULUS-RESPONSE COUPLING IN ENDOTHELIAL-CELLS
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DOI：
10.1161/01.hyp.21.1.112
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发表时间：
1993-01-01
期刊：
影响因子：
8.3
通讯作者：
STRAUSS, HC
中科院分区：
文献类型：
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作者：
HIMMEL, HM;WHORTON, AR;STRAUSS, HC
血管内皮似乎是一个独特的器官。它不仅对许多激素和化学信号作出反应，而且还感知物理参数的变化，如剪切应力，产生调节许多细胞反应的介质，包括血管平滑肌，血小板和白细胞。在许多情况下，内皮细胞对这些不同信号的初始反应涉及胞质Ca 2+的升高和Ca 2+依赖性酶的激活，包括一氧化氮合酶和磷脂酶A2。Ca 2+从细胞内储存（最可能是内质网）释放和Ca 2+从细胞外空间流入都有助于[Ca 2 +]i增加。Ca 2+释放的最重要的触发剂是肌醇1，4，5-三磷酸，它是由磷脂酶C的作用产生的，磷脂酶C是一种质膜酶，在许多情况下由受体-G蛋白级联激活。Ca 2+内流似乎与受体-G蛋白-酶复合物的活性和内质网的充实程度有关，但不涉及电压门控Ca 2+通道。Ca 2+内流的大小取决于电化学梯度，其由膜电位V（m）调节。在基础条件下，V（m）是由一个大的内向整流K+电流。一些刺激，例如，乙酰胆碱，已被证明能使V（m）升高，从而增加Ca 2+的电化学梯度，这似乎是通过激活Ca 2+依赖性K+和Cl-电流来调节的。然而，对于许多描述或假设的通道（例如，非选择性阳离子通道，Ca 2+激活的Cl-通道）使得评估它们对内皮细胞功能的作用相当困难。未来可能的研究方向和临床意义进行了讨论。
Vascular endothelium appears to be a unique organ. It not only responds to numerous hormonal and chemical signals but also senses changes in physical parameters such as shear stress, producing mediators that modulate the responses of numerous cells, including vascular smooth muscle, platelets, and leukocytes. In many cases, the initial response of endothelial cells to these diverse signals involves elevation of cytosolic Ca2+ and activation of Ca2+-dependent enzymes, including nitric oxide synthase and phospholipase A2. Both the release of Ca2+ from intracellular stores, most likely the endoplasmic reticulum, and the influx of Ca2+ from the extracellular space contribute to the [Ca2+]i increase. The most important trigger for Ca2+ release is inositol 1,4,5-trisphosphate, which is generated by the action of phospholipase C, a plasmalemmal enzyme activated in many cases by the receptor-G protein cascade. Ca2+ influx appears to be related to the activity of receptor-G protein-enzyme complex and to the degree of fullness of the endoplasmic reticulum but does not involve voltage-gated Ca2+ channels. The magnitude of the Ca2+ influx depends on the electrochemical gradient, which is modulated by the membrane potential, V(m). Under basal conditions, V(m) is dominated by a large inward rectifier K+ current. Some stimuli, e.g., acetylcholine, have been shown to hyperpolarize V(m), thus increasing the electrochemical gradient for Ca2+, which appears to be modulated by activation of Ca2+-dependent K+ and Cl- currents. However, the lack of potent and specific blockers for many of the described or postulated channels (e.g., nonselective cation channel, Ca2+-activated Cl- channel) makes an estimation of their effect on endothelial cell function rather difficult. Possible future directions of research and clinical implications are discussed.