Cytoplasmic cAMP concentrations in intact cardiac myocytes

diac myocytes there is evidence that activation of some receptors can regulate protein kinase A (PKA)-dependent responses by stimulating cAMP production that is limited to discrete intracellular domains. We previously developed a computational model of compartmentalized cAMP signaling to investigate the feasibility of this idea. The model was able to reproduce experimental results demonstrating that both 1-adrenergic and M2 muscarinic receptor-mediated cAMP changes occur in microdomains associated with PKA signaling. However, the model also suggested that the cAMP concentration throughout most of the cell could be significantly higher than that found in PKA-signaling domains. In the present study we tested this counterintuitive hypoth-esis using a freely diffusible fluorescence resonance energy transfer-based biosensor constructed from the type 2 exchange protein acti-vated by cAMP (Epac2-camps). It was determined that in adult ventricular myocytes the basal cAMP concentration detected by th