β-Adrenoceptor redistribution impairs NO/cGMP/PDE2 signalling in failing cardiomyocytes.

Cardiomyocyte β-adrenoceptors (β-ARs) coupled to soluble guanylyl cyclase (sGC)-dependent production of the second messenger 3',5'-cyclic guanosine monophosphate (cGMP) have been shown to protect from heart failure. However, the exact localization of these receptors to fine membrane structures and subcellular compartmentation of β-AR/cGMP signals underpinning this protection in health and disease remain elusive. Here, we used a Förster Resonance Energy Transfer (FRET)-based cGMP biosensor combined with scanning ion conductance microscopy (SICM) to show that functional β-ARs are mostly confined to the T-tubules of healthy rat cardiomyocytes.