Abstract 14993: Alteration in b2-ARs Dependent cAMP Signalling Linked to Post Infarction Remodelling of T-tubules in Rat Cardiomyocytes

The T-tubule (TT) network of cardiomyocytes (CMs) compartmentalizes beta-2 adrenergic receptor (β2AR) signalling allowing stringent control of spread of cAMP. In heart failure these structures are disrupted, disturbing cAMP compartmentalization, with TT loss and associated changes in cAMP signalling occurring in a stepwise manner. We studied these changes at different stages of disease progression. Ventricular CMs were isolated from post-myocardial infarction (MI) failing rats at 4 weeks (compensated), 8 and 16 weeks (decompensated). TT density, regularity, and axial junctions were determined by confocal imaging of di-8-ANNEPS stained CMs. Scanning Ion Conductance Microscopy (SICM) generated CM scans allowed assessment of topographical features. cAMP levels were determined using a FRET sensor combined with SICM. β2AR were stimulated with isoproterenol with a β1-specific antagonist CGP20712A, by whole cell perfusion, or locally via SICM nanopipette. NKH477 an adenylate cyclase (AC) activator was applied su...