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Science:β2ARs所产生的cAMP信号与心力衰竭有关

来源:EurekAlert! 2010-03-01 17:09

专题:Science报道

据2月26日的《科学》杂志报道说, 心肌细胞被一种叫做β1- 和 β2-肾上腺素能受体 (βARs)的专门化的信号分子所覆盖,这些受体的活动对心脏功能来说是极为重要的。但新的研究显示,这些受体中的某一种的空间分布的变化也许会促成心力衰竭。

这一发现是由Viacheslav Nikolaev及其同僚将高倍显微镜与活细胞扫描离子电导显微镜相结合来研究大鼠与小鼠的心肌细胞时所作出的。 他们发现,在健康的心肌细胞中,β2ARs局限在被称作横小管的缝隙之中,因此,它们是在细胞的某些局部地区产生信号产物cAMP的。

然而,在那些罹患心力衰竭的老鼠细胞中,人们发现其β2ARs分布在整个细胞的表面,因而会产生出弥散的cAMP信号。 研究人员提示,β2ARs所产生的cAMP信号的空间分布可能在心力衰竭上扮演着一个重要的角色。他们的发现也许会在将来使人们更好地了解心脏病。(生物谷Bioon.com)

生物谷推荐原始出处:

Science February 25, 2010 DOI: 10.1126/science.1185988

β2-Adrenergic Receptor Redistribution in Heart Failure Changes cAMP Compartmentation

Viacheslav O. Nikolaev,1 Alexey Moshkov,1 Alexander R. Lyon,1 Michele Miragoli,1 Pavel Novak,1,2 Helen Paur,1 Martin J. Lohse,3 Yuri E. Korchev,2 Sian E. Harding,1 Julia Gorelik1,*

1 Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK.
2 Division of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
3 Institute of Pharmacology and Toxicology and Rudolf-Virchow-Center, University of Würzburg, Versbacher Strasse 9, Würzburg 97078, Germany.

The β1- and β2-adrenergic receptors (βARs) on the surface of cardiomyocytes mediate distinct effects on cardiacfunction and the development of heart failure by regulating production of the second messenger adenosine 3',5'-monophosphate (cAMP). The spatial localization in cardiomyocytes of these βARs, which are coupled toheterotrimeric guanine nucleotide–binding protein (G protein), and the functional implications of their localization have been unclear. We combined nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy techniques and found that, in cardiomyocytes from healthy adult rats and mice, spatially confined β2AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional β1ARs are distributed across the entire cell surface. In cardiomyocytes derived from a rat model of chronic heartfailure, β2ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediatedcAMP signaling.Thus,the redistribution of β2ARs in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype.

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