Fig. 8.

β-AR–induced cAMP signals at SR and OMM compartments were impaired in HF and Mfn2 KD SANCs. (A and B) Schematic of the SR-targeted FRET-based PKA reporter. Confocal images of SANs expressing SR-AKAR3 show the localization of the biosensor. (C and D) Time course of changes in the magnitude of normalized FRET responses (R/R₀) in SANCs expressing SR-AKAR3 and OMM-AKAR3 upon application of β-AR agonist isoproterenol (iso, 100 nM) in the presence of the adenylyl cyclase activator forskolin (fsk) and phosphodiesterase inhibitor IBMX in sham and HF cells (C) or control and Mfn2 KD SANCs (D). Bar graphs that represent the maximal increases in the FRET ratio of these sensors are plotted. n ≥ 5 cells from three preparations per condition. Data represent the mean ± SEM. *P < 0.05 by Kruskal–Wallis with Dunn’s multiple comparisons.