Imperial College London
Alternate

DrAlexanderLyon

Faculty of Medicine, National Heart & Lung Institute

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3409a.lyon Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Nikolaev:2010:10.1126/science.1185988,
author = {Nikolaev, VO and Moshkov, A and Lyon, AR and Miragoli, M and Novak, P and Paur, H and Lohse, MJ and Korchev, YE and Harding, SE and Gorelik, J},
doi = {10.1126/science.1185988},
journal = {Science (New York, N.Y.)},
pages = {1653--7},
title = {Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation.},
url = {http://dx.doi.org/10.1126/science.1185988},
volume = {327},
year = {2010}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP). The spatial localization in cardiomyocytes of these betaARs, which are coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins), 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 beta2AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional beta1ARs are distributed across the entire cell surface. In cardiomyocytes derived from a rat model of chronic heart failure, beta2ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP signaling. Thus, the redistribution of beta(2)ARs in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype.
AU  - Nikolaev,VO
AU  - Moshkov,A
AU  - Lyon,AR
AU  - Miragoli,M
AU  - Novak,P
AU  - Paur,H
AU  - Lohse,MJ
AU  - Korchev,YE
AU  - Harding,SE
AU  - Gorelik,J
DO  - 10.1126/science.1185988
EP  - 7
PY  - 2010///
SP  - 1653
TI  - Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation.
T2  - Science (New York, N.Y.)
UR  - http://dx.doi.org/10.1126/science.1185988
UR  - http://www.sciencemag.org/content/327/5973/1653.abstract
VL  - 327
ER  -
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