Different cAMP nanodomains execute βAR signaling in cardiomyocytes
When βARs are activated, ACs produce cAMP, which diffuses throughout the cytosol. Different cAMP nanodomains help to ensure cAMP signaling specificity. PDEs and AKAPs are two important components of cAMP nanodomains. PDEs degrade cAMP, helping to form cAMP gradients within the cell. AKAPs anchor PKA, a key cAMP effector protein, to specific locations within the cell. Both PDEs and AKAPs have multiple isoforms with varying enzymatic activity, localization, and expression levels. The presence of multiple cAMP signaling components helps ensure that the correct cellular effects are achieved upon βAR activation. Abbrreviations: AC, adenylyl cyclase; AKAP: A-kinase anchoring protein; βAR, β adrenergic receptor; EPAC, exchange protein directly activated by cAMP; PDE, phosphodiesterase; PKA, protein kinase A; PMCA, plasma membrane calcium ATPase; LTCC, L-type calcium channel; RyR, Ryanodine channel; SERCA, SR calcium ATP-ase, SR, sarcoplasmic reticulum.