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跨膜钠/钾泵调节血小板体积和反应性的模型。

Model for the regulation of platelet volume and responsiveness by the trans-membrane Na+/K(+)-pump.

作者信息

Marx G, Blankenfeld A, Panet R, Gorodetsky R

机构信息

New York Blood Center, NY 10021.

出版信息

J Cell Physiol. 1992 May;151(2):249-54. doi: 10.1002/jcp.1041510205.

DOI:10.1002/jcp.1041510205
PMID:1315320
Abstract

The correspondence between K+ uptake in platelets to their responsiveness was studied using 86Rb+ as an analogue of K+. An average 86Rb+ uptake rate of 0.73 (+/- 0.140) x 10(-15) mole Rb+/min-plt (n = 20) was observed. By the use of K(+)-influx inhibitors, we were able to distinguish three distinct 86Rb+ uptake pathways: an ouabain-sensitive (61% +/- 2% inhibitable) pump and two equivalent channels, only one of which is sensitive to furosemide. Other platelet parameters were also examined in conjunction with K(+)-uptake. Platelets incubated with ouabain exhibited an overall rise in their cell volume (MPV) with incubation time (delta MPV = 7.4 x 10(-17) L/min-1 plt-1). Concomitantly, over 24 hours, a steady decrease in platelet number was recorded by blood cell coulter, which correlated inversely with the counts of particles, which by their size resemble white blood cells (r = 0.89). On a cellular level, incubation with ouabain induced greater expression of surface fibrinogen-receptor (GPIIb), increased binding of FITC-labelled fibrinogen, and increased responsiveness to ADP. Our observations suggest the following sequence of events: Ouabain turns off the Na+/K(+)-ATPase pump, which leads to water accumulation in platelets and concomitant increased MPV. Greater expression of fibrinogen receptors on the distended platelet surface corresponds to spontaneous microaggregate formation as well as greater responsiveness to agonists. Our model links volume regulation, the expression of fibrinogen receptors, and the sensitivity of platelets to agonists to the activity of the Na+/K(+)-ATPase pump.

摘要

利用⁸⁶Rb⁺作为K⁺的类似物,研究了血小板对K⁺的摄取与其反应性之间的关系。观察到⁸⁶Rb⁺的平均摄取速率为0.73(±0.140)×10⁻¹⁵摩尔Rb⁺/分钟·血小板(n = 20)。通过使用K⁺内流抑制剂,我们能够区分三种不同的⁸⁶Rb⁺摄取途径:一种哇巴因敏感的(可被抑制61%±2%)泵和两个等效通道,其中只有一个对呋塞米敏感。还结合K⁺摄取检查了其他血小板参数。用哇巴因孵育的血小板其细胞体积(平均血小板体积)随孵育时间总体增加(平均血小板体积变化量 = 7.4×10⁻¹⁷升/分钟⁻¹·血小板⁻¹)。同时,在24小时内,血细胞计数器记录到血小板数量稳步下降,这与大小类似白细胞的颗粒计数呈负相关(r = 0.89)。在细胞水平上,用哇巴因孵育诱导表面纤维蛋白原受体(糖蛋白IIb)表达增加、异硫氰酸荧光素标记的纤维蛋白原结合增加以及对ADP的反应性增加。我们的观察结果提示了以下一系列事件:哇巴因关闭Na⁺/K⁺-ATP酶泵,这导致血小板内水的蓄积并伴随平均血小板体积增加。扩张的血小板表面上纤维蛋白原受体的表达增加对应于自发微聚集体的形成以及对激动剂的更大反应性。我们的模型将体积调节、纤维蛋白原受体的表达以及血小板对激动剂的敏感性与Na⁺/K⁺-ATP酶泵的活性联系起来。

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