Ca(2+) entry in endothelial cells is a key signaling event as it prolongs the Ca(2+) signal activated by a receptor agonist, and thus allows an adequate production of a variety of compounds. The possible routes that lead to Ca(2+) entry in non-excitable cells include the receptor-activated Ca(2+) entry (RACE), which requires the presence of an agonist to be activated, and the store-operated Ca(2+) entry (SOCE) pathway, whose activation requires the depletion of the ER Ca(2+) store. However, the relative importance of these two influx pathways during physiological stimulation is not known. In the present study we experimentally differentiated these two types of influxes and determined under which circumstances they are activated. We show that La(3+) (at 10 microM) is a discriminating compound that efficiently blocks SOCE but is almost without effect on histamine-induced Ca(2+) entry (RACE). In line with this, histamine does not induce massive store depletion when performed in the presence of extracellular Ca(2+). In addition, inhibition of mitochondrial respiration significantly reduces SOCE but modestly affects RACE. Thus, agonist-induced Ca(2+) entry is insensitive to La(3+), and only modestly affected by mitochondrial depolarization. These data shows that agonist relies almost exclusively on RACE for sustained Ca(2+) signaling in endothelial cells.

中文翻译：

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有证据表明受体激活的 Ca2+ 进入途径独立于 Ca2) 在内皮细胞中储存消耗。

Ca(2+) 进入内皮细胞是一个关键的信号事件，因为它延长了由受体激动剂激活的 Ca(2+) 信号，因此可以充分生产各种化合物。导致 Ca(2+) 进入不可兴奋细胞的可能途径包括受体激活的 Ca(2+) 进入 (RACE)，这需要激动剂的存在才能被激活，以及储存操作的 Ca( 2+) 进入 (SOCE) 途径，其激活需要消耗 ER Ca(2+) 存储。然而，这两种流入途径在生理刺激期间的相对重要性尚不清楚。在本研究中，我们通过实验区分这两种类型的流入，并确定它们在何种情况下被激活。我们表明La(3+) （在10 microM） 是有效地阻止SOCE 但对组胺诱导的Ca(2+) 条目(RACE) 几乎没有影响的区别化合物。与此一致，在存在细胞外 Ca(2+) 的情况下进行时，组胺不会导致大量储存耗尽。此外，线粒体呼吸的抑制会显着降低 SOCE，但会适度影响 RACE。因此，激动剂诱导的 Ca(2+) 条目对 La(3+) 不敏感，并且仅受到线粒体去极化的适度影响。这些数据表明，激动剂几乎完全依赖于 RACE 在内皮细胞中持续的 Ca(2+) 信号传导。线粒体呼吸的抑制会显着降低 SOCE，但会适度影响 RACE。因此，激动剂诱导的 Ca(2+) 条目对 La(3+) 不敏感，并且仅受到线粒体去极化的适度影响。这些数据表明，激动剂几乎完全依赖于 RACE 在内皮细胞中持续的 Ca(2+) 信号传导。线粒体呼吸的抑制会显着降低 SOCE，但会适度影响 RACE。因此，激动剂诱导的 Ca(2+) 条目对 La(3+) 不敏感，并且仅受到线粒体去极化的适度影响。这些数据表明，激动剂几乎完全依赖于 RACE 在内皮细胞中持续的 Ca(2+) 信号传导。