Subcellular Compartmentalization of Cyclic Adenosine Monophosphate in Heart Failure and Inotropic Pharmacology

Cyclic adenosine monophosphate (cAMP) is a second messenger downstream of many G-protein coupled receptors, including the β1-adrenoceptor, which is the target of many clinically used inotropic agents. When the Gαs subunit of a heterotrimeric G-protein is activated, it causes a localized elevation of cAMP. The significance of the spatial distribution of the elevation in cAMP is increasingly recognized, as is the disturbance of these microdomains in diseased states. Herein, the spatial compartmentalization of inotropic signaling is explored, including from internalized receptors.