Figure 1.

cGMP compartmentation in CMs. There are at least two different cGMP pools: the NP/pGC/cGMP pool formed at the plasma membrane, and the NO/sGC/cGMP pool which can be controlled by the β₃-adrenergic receptor (β₃-AR) at the cell surface caveolae. pGC/cGMP is tightly controlled by PDE2 and PDE9, while sGC/cGMP pool is predominantly regulated by PDE5 and PDE3. PKG I is one of the major downstream targets for cGMP signaling. NO/sGC stimulated PKG I is known to phosphorylate and inhibit PDE5. ANP/pGC stimulated PKG I can be recruited to the plasma membrane and is assumed to modulate GC-A activity. Black arrows indicate enzymatic activity, dotted arrows indicate protein action.