Function of Adenylyl Cyclase in Heart: the AKAP Connection

Cyclic adenosine monophosphate (cAMP), synthesized by adenylyl cyclase (AC), is a universal second messenger that regulates various aspects of cardiac physiology from contraction rate to the initiation of cardioprotective stress response pathways. Local pools of cAMP are maintained by macromolecular complexes formed by A-kinase anchoring proteins (AKAPs). AKAPs facilitate control by bringing together regulators of the cAMP pathway including G-protein-coupled receptors, ACs, and downstream effectors of cAMP to finely tune signaling. This review will summarize the distinct roles of AC isoforms in cardiac function and how interactions with AKAPs facilitate AC function, highlighting newly appreciated roles for lesser abundant AC isoforms.