%0 Journal Article %1 Nikolaev2010 %A Nikolaev, V. O. %A Moshkov, A. %A Lyon, A. R. %A Miragoli, M. %A Novak, P. %A Paur, H. %A Lohse, M. J. %A Korchev, Y. E. %A Harding, S. E. %A Gorelik, J. %D 2010 %J Science %K AMP-Dependent AMP/*metabolism Animals Cardiac/*metabolism/ultrastructure Cell Chronic Compartmentation Cyclic Cytosol/metabolism Disease Energy Failure/*metabolism/*pathology Fluorescence Heart Kinases/metabolism Knockout Male Membrane/*metabolism/ultrastructure Mice Microscopy/methods Myocytes, Protein Rats Resonance Sarcolemma/*metabolism/ultrastructure Signal Sprague-Dawley Transduction Transfer Transgenic beta-1/genetics/metabolism beta-2/genetics/*metabolism Receptor Adrenergic %N 5973 %P 1653-7 %T Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation %U http://www.ncbi.nlm.nih.gov/pubmed/20185685 %V 327 %X 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.

@article{Nikolaev2010, abstract = {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.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Nikolaev, V. O. and Moshkov, A. and Lyon, A. R. and Miragoli, M. and Novak, P. and Paur, H. and Lohse, M. J. and Korchev, Y. E. and Harding, S. E. and Gorelik, J.}, biburl = {https://www.bibsonomy.org/bibtex/2d5b7e044587cfdd3dc7b4997c06e7730/pharmawuerz}, endnotereftype = {Journal Article}, groups = {private}, interhash = {e7c0b77debeed943e71531faca425062}, intrahash = {d5b7e044587cfdd3dc7b4997c06e7730}, issn = {1095-9203 (Electronic) 0036-8075 (Linking)}, journal = {Science}, keywords = {AMP-Dependent AMP/*metabolism Animals Cardiac/*metabolism/ultrastructure Cell Chronic Compartmentation Cyclic Cytosol/metabolism Disease Energy Failure/*metabolism/*pathology Fluorescence Heart Kinases/metabolism Knockout Male Membrane/*metabolism/ultrastructure Mice Microscopy/methods Myocytes, Protein Rats Resonance Sarcolemma/*metabolism/ultrastructure Signal Sprague-Dawley Transduction Transfer Transgenic beta-1/genetics/metabolism beta-2/genetics/*metabolism Receptor Adrenergic}, month = {Mar 26}, note = {Nikolaev, Viacheslav O Moshkov, Alexey Lyon, Alexander R Miragoli, Michele Novak, Pavel Paur, Helen Lohse, Martin J Korchev, Yuri E Harding, Sian E Gorelik, Julia 084064/Wellcome Trust/United Kingdom Biotechnology and Biological Sciences Research Council/United Kingdom Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't United States Science (New York, N.Y.) Science. 2010 Mar 26;327(5973):1653-7. Epub 2010 Feb 25.}, number = 5973, pages = {1653-7}, shorttitle = {Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation}, timestamp = {2010-12-14T18:22:56.000+0100}, title = {Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20185685}, volume = 327, year = 2010 }