Abstract
Cardiac myocytes have provided a key paradigm for the concept of the
compartmentalized cAMP generation sensed by AKAP-anchored PKA. Phosphodiesterases
(PDEs) provide the sole route for degrading cAMP in cells and are
thus poised to regulate intracellular cAMP gradients. PDE3 and PDE4
represent the major cAMP degrading activities in rat ventriculocytes.
By performing real-time imaging of cAMP in situ, we establish the
hierarchy of these PDEs in controlling cAMP levels in basal conditions
and on stimulation with a beta-adrenergic receptor agonist. PDE4,
rather than PDE3, appears to be responsible for modulating the amplitude
and duration of the cAMP response to beta-agonists. PDE3 and PDE4
localize to distinct compartments and this may underpin their different
functional roles. Our findings indicate the importance of distinctly
localized PDE isoenzymes in determining compartmentalized cAMP signaling.
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