Activators of potassium channels enhance calcium influx into endothelial cells as a consequence of potassium currents
Activators of potassium channels enhance calcium influx into endothelial cells as a consequence of potassium currents
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由于钾电流，钾通道激活剂可增强钙流入内皮细胞
DOI：
10.1007/bf00178979
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
R. Busse
中科院分区：
文献类型：
--
作者：
A. Lückhoff;R. Busse
ca2 +内流到受刺激的内皮细胞通过去极化减弱。我们假设Ca2+内流是由膜电位驱动的，并可能通过K+通道激活剂等超极化药物增强。因此，我们研究了pinacidil、cromakalim和环氨酸对培养的猪主动脉内皮细胞膜电流和胞内游离钙浓度（[Ca2+]i）的影响。在膜片夹持细胞中，pinacidil （1 μmol/l）和cromakalim （1 μmol/l）诱导了由K+携带的外向电流，并显著延长了缓激肽和ATP诱导的Ca2+依赖性K+电流。缓激肽反应的峰值电流不受影响。在携带荧光Ca2+指示剂indo-1和硫柳汞预刺激的细胞中，pinacidil （0.1-1 μmol/l）引起[Ca2+)i从100±10到550±110 nmol/l的长期增加。这些影响在含有90mmol /l K+的培养基中完全消除。用cromakalim得到了类似的结果。同样，在缓激肽刺激的细胞中，当在初始峰值后[Ca2+]i下降期间使用pinacidil时，[Ca2+]i升高。环氨酸在静息细胞中激发K+电流，在缓激素刺激的细胞中减弱K+电流。即使在缺乏细胞外Ca2+和富K+的培养基中，它也会升高[Ca2+]i。因此，环氨酸的作用不能用对K+通道的直接作用来解释。然而，我们的研究表明，pinacidil和cromakalim通过诱导超极化和增强电位依赖性Ca2+内流的驱动力，提高了K+通道激活后的[Ca2+]i。通过这种方式，两种药物可能促进Ca2+依赖性的内皮源性放松因子的形成。
SummaryCa2+ influx into stimulated endothelial cells is attenuated by depolarization. We hypothesized that Ca2+ influx is driven by the membrane potential and may be enhanced by hyperpolarizing drugs like activators of K+ channels. Therefore we studied the effects of pinacidil, cromakalim, and cicletanine on membrane currents and on the intracellular free calcium concentration ([Ca2+]i) in cultured endothelial cells from porcine aorta. In patch-clamped cells, pinacidil (1 μmol/l) and cromakalim (1 μmol/l) elicited outward currents carried by K+ and significantly prolonged the Ca2+-dependent K+ currents induced by bradykinin and ATP. Peak currents in response to bradykinin were not affected. In cells loaded with the fluorescent Ca2+ indicator indo-1 and prestimulated with thimerosal, pinacidil (0.1–1 μmol/l elicited long-lasting increases in [Ca2+)i from 100 ± 10 to 550 ± 110 nmol/l. These effects were completely abolished in a medium containing 90 mmol/l K+. Similar results were obtained with cromakalim. Likewise, in cells stimulated with bradykinin, pinacidil raised [Ca2+]i when applied during the decline of [Ca2+]i after the initial peak. Cicletanine elicited K+ currents in resting and attenuated K+ currents in bradykinin-stimulated cells. It elevated [Ca2+]i even in the absence of extracellular Ca2+ and in K+-rich medium. Hence, the effects of cicletanine cannot be explained by direct actions on K+ channels. However, our studies demonstrate that pinacidil and cromakalim elevate [Ca2+]i secondary to their activation of K+ channels by inducing hyperpolarization and augmenting the driving force for potential-dependent Ca2+ influx. In this way, the two drugs may promote Ca2+-dependent formation of endothelium-derived relaxing factor.
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发表时间：
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期刊：
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DOI：
10.1016/s0021-9258(18)51563-5
发表时间：
1989-08
期刊：
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