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首页> 外文期刊>Progress in Biophysics and Molecular Biology: An International Review Journal >Studying beta(1) and beta(2) adrenergic receptor signals in cardiac cells using FRET-based sensors
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Studying beta(1) and beta(2) adrenergic receptor signals in cardiac cells using FRET-based sensors

机译：使用FRET的传感器研究心脏细胞中的β（1）和β（2）肾上腺素能受体信号

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Cyclic 3'-5' adenosine monophosphate (cAMP) is a key modulator of cardiac function. Thanks to the sophisticated organization of its pathway in distinct functional units called microdomains, cAMP is involved in the regulation of both inotropy and chronotropy as well as transcription and cardiac death. While visualization of cAMP microdomains can be achieved thanks to cAMP-sensitive FRET-based sensors, the molecular mechanisms through which cAMP-generating stimuli are coupled to distinct functional outcomes are not well understood. One possibility is that each stimulus activates multiple microdomains in order to generate a spatiotemporal code that translates into function. To test this hypothesis here we propose a series of experimental protocols that allow to simultaneously follow cAMP or Protein Kinase A (PKA)-dependent phosphorylation in different subcellular compartments of living cells. We investigate the responses of beta Adrenergic receptors (beta(1)AR and beta(2)AR) challenged with selective drugs that enabled us to measure the actions of each receptor independently. At the whole cell level, we used a combination of co-culture with selective beta AR stimulation and were able to molecularly separate cardiac fibroblasts from neonatal rat ventricular myocytes based on their cAMP responses. On the other hand, at the subcellular level, these experimental protocols allowed us to dissect the relative weight of beta(1) and beta 2 adrenergic receptors on cAMP signalling at the cytosol and outer mitochondrial membrane of NRVMs. We propose that experimental procedures that allow the collection of multiparametric data are necessary in order to understand the molecular mechanisms underlying the coupling between extracellular signals and cellular responses. (C) 2019 Elsevier Ltd. All rights reserved.
机译：循环3'-5'腺苷一磷酸盐（CAMP）是心功能的关键调节剂。由于其途径的复杂组织，以众生的功能单位称为微摩粉，阵营参与了尿素和时际功能​​的调节以及转录和心脏死亡。虽然营养敏感的FRET的传感器可以实现CAMP微摩托的可视化，但是营养产生刺激的分子机制并不了解不同的功能结果。一种可能性是每个刺激激活多个微差点，以便生成转化为功能的时空代码。为了测试该假设，我们提出了一系列实验方案，其允许在不同亚细胞的活细胞中同时遵循营养蛋白或蛋白激酶A（PKA）依赖性磷酸化。我们研究了β肾上腺素能受体（β（1）AR和Beta（2）AR）的反应，这些反应挑战了选择性药物，使我们能够独立地测量每个受体的行为。在整个细胞水平，我们使用共同培养的组合与选择性β刺激，并且能够基于其阵营的反应来分解来自新生大鼠心室肌细胞的心脏成纤维细胞。另一方面，在亚细胞水平，这些实验方案允许我们将β（1）和β2肾上腺素能受体对NRVMS的细胞溶胶和外部线粒体膜的阵地信号传导的相对重量剖析。我们提出了允许收集多次数据的实验程序是必要的，以便理解细胞外信号与细胞反应之间的偶联的分子机制。 （c）2019年elestvier有限公司保留所有权利。

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