IARC, a novel arachidonate-regulated, noncapacitative Ca2+ entry channel
IARC, a novel arachidonate-regulated, noncapacitative Ca2+ entry channel
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DOI：
10.1074/jbc.275.13.9114
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发表时间：
2000-03-31
影响因子：
4.8
通讯作者：
Shuttleworth, TJ
中科院分区：
文献类型：
--
作者：
Mignen, O;Shuttleworth, TJ
随着肌醇三磷酸诱导释放储存的 Ca2+，受体增强的 Ca2+ 进入是细胞内 Ca2+ 信号的关键组成部分，该信号由作用于受体的激动剂与磷脂酶 C 的激活偶联产生。尽管已知细胞内 Ca2+ 储存的简单清空能够通过所谓的“电容”机制激活 Ca2+ 进入，但最近的证据表明，生理激动剂浓度下的 Ca2+ 进入，其中振荡通常观察到 Ca2+ 信号，但不符合这样的模型。相反，由花生四烯酸调节的非电容性 Ca2+ 进入途径似乎负责这些条件下的 Ca2+ 进入。使用全细胞膜片钳技术，我们证明低浓度的花生四烯酸激活 Ca2+ 选择性电流，该电流表面上类似于存储操作电流 I-CRAC，但也表现出某些独特的特征。我们将这种新型电流命名为 I-ARC（花生四烯酸调节钙电流）。重要的是，I-arc 在 Ca2+ 储备已最大限度耗尽的细胞中很容易被激活。 I-ARC 代表了一种新颖的 Ca2+ 进入途径，该途径完全独立于储存耗尽所激活的途径，并且在生理刺激水平下被特异性激活。
Along with the inositol trisphosphate-induced release of stored Ca2+, a receptor-enhanced entry of Ca2+ is a critical component of intracellular Ca2+ signals generated by agonists acting at receptors coupled to the activation of phospholipase C. Although the simple emptying of the intracellular Ca2+ stores is known to be capable of activating Ca2+ entry via the so-called "capacitative" mechanism, recent evidence suggests that Ca2+ entry at physiological agonist concentrations, where oscillatory Ca2+ signals are typically observed, does not conform to such a model. Instead, a noncapacitative Ca2+ entry pathway regulated by arachidonic acid appears to be responsible for Ca2+ entry under these conditions. Using whole-cell patch clamp techniques we demonstrate that low concentrations of arachidonic acid activate a Ca2+-selective current that is superficially similar to the store-operated current I-CRAC, but which also demonstrates certain distinct features. We have named this novel current I-ARC (for arachidonate-regulated calcium current). Importantly, I-arc can be readily activated in cells whose Ca2+ stores have been maximally depleted. I-ARC represents a novel Ca2+ entry pathway that is entirely separate from those activated by store depletion and is specifically activated at physiological levels of stimulation.