TY - JOUR
T1 - β2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation
AU - Nikolaev, Viacheslav O.
AU - Moshkov, Alexey
AU - Lyon, Alexander R.
AU - Miragoli, Michele
AU - Novak, Pavel
AU - Paur, Helen
AU - Lohse, Martin J.
AU - Korchev, Yuri E.
AU - Harding, Sian E.
AU - Gorelik, Julia
PY - 2010/3/26
Y1 - 2010/3/26
N2 - The β1- and β2-adrenergic receptors (βARs) 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 βARs, 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 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 heart failure, β2ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP signaling. Thus, the redistribution of β2ARs in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype.
AB - The β1- and β2-adrenergic receptors (βARs) 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 βARs, 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 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 heart failure, β2ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP 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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U2 - 10.1126/science.1185988
DO - 10.1126/science.1185988
M3 - Article
C2 - 20185685
AN - SCOPUS:77950286813
VL - 327
SP - 1653
EP - 1657
JO - Science
JF - Science
SN - 0036-8075
IS - 5973
ER -