In the light of the knowledge accumulated over the years, it becomes clear that intracellular cAMP is not uniformly distributed within cardiomyocytes and that cAMP compartmentation is required for adequate processing and targeting of the information generated at the membrane. Localized cAMP signals may be generated by interplay between discrete production sites and restricted diffusion within the cytoplasm. In addition to specialized membrane structures that may limit cAMP spreading, degradation of the second messenger by cyclic nucleotide phosphodiesterases (PDEs) appears critical for the formation of dynamic microdomains that confer specificity of the response to various hormones. This review will cover the role of the different cAMP-PDE isoforms in this process. This article is part of a Special Issue entitled "Local Signaling in Myocytes."
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