β 2 -Adrenergic Receptor Redistribution in Heart Failure Changes cAMP Compartmentation

Abstract

Heart Cell Signaling in 3D A healthy heart relies on the proper transduction of cellular signals through the β 1 - and β 2 -adrenergic receptors (βARs), which are located on the surface of the heart's muscle cells (cardiomyocytes). The surface of these cells resembles a highly organized series of hills and valleys and it has been unclear whether this topography plays a role in the βAR signaling events that are critical to cell function. Nikolaev et al. (p. 1653 , published online 25 February; see Perspective by Dorn ) monitored the cyclic adenosine monophosphate (cAMP) signals generated by the βARs in living cardiomyocytes. In cells from healthy rats and from rats with heart failure, the β 1 ARs were localized across the entire cell surface. In contrast, the spatial localization of the β 2 ARs differed in healthy and failing cells. In healthy cardiomyocytes, the β 2 ARs resided exclusively within surface invaginations called transverse tubules, thereby producing spatially confined cAMP signals, whereas in failing cardiomyocytes, the β 2 ARs redistributed to other cell surface areas, thereby producing diffuse cAMP signals. Thus, changes in the spatial localization of β 2 AR-induced cAMP signaling may contribute to heart failure.