Decoding dynamic Ca(2+) signaling in the vascular endothelium.

Decoding dynamic Ca(2+) signaling in the vascular endothelium.
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解码血管内皮细胞中的动态 Ca(2+) 信号传导。

DOI:
10.3389/fphys.2014.00447
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发表时间:
2014
影响因子:
4
通讯作者:
Francis M
Francis M
中科院分区:
医学2区
文献类型:
--
作者:
Taylor MS;Francis M

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尽管急性和慢性血管调节本质上是由内皮细胞钙离子驱动的,但对钙依赖信号的控制和靶向却知之甚少。最近的研究揭示了局部和动态的内皮钙事件组成了一个复杂的沿血管内膜的信号网络。从内钙通道和质膜阳离子通道产生的离散的钙瞬变与特定的膜K+通道偶联,促进内皮细胞超极化和血管扩张。这些信号的时空调节,而不是全球钙离子升高,似乎在生理条件下指导内皮功能。事实上,动态钙信号模式的改变可能是各种心血管疾病的基本内皮功能障碍的基础。近年来,成像方法和分析的进步使得对完整内皮细胞内钙动力学的详细检测、定量和评估成为可能。在这里,我们讨论对这些信号的最新见解,包括它们的来源和功能编码。我们还讨论了数据获取和解释的关键方面,包括自动化高含量分析的广泛应用。
Although acute and chronic vasoregulation is inherently driven by endothelial Ca2+, control and targeting of Ca2+-dependent signals are poorly understood. Recent studies have revealed localized and dynamic endothelial Ca2+ events comprising an intricate signaling network along the vascular intima. Discrete Ca2+ transients emerging from both internal stores and plasmalemmal cation channels couple to specific membrane K+ channels, promoting endothelial hyperpolarization and vasodilation. The spatiotemporal tuning of these signals, rather than global Ca2+ elevation, appear to direct endothelial functions under physiologic conditions. In fact, altered patterns of dynamic Ca2+ signaling may underlie essential endothelial dysfunction in a variety of cardiovascular diseases. Advances in imaging approaches and analyses in recent years have allowed for detailed detection, quantification, and evaluation of Ca2+ dynamics in intact endothelium. Here, we discuss recent insights into these signals, including their sources of origination and their functional encoding. We also address key aspects of data acquisition and interpretation, including broad applications of automated high-content analysis.
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