Compartmentalized cAMP signaling in cardiac ventricular myocytes

Activation of different receptors that act by generating the common second messenger cyclic adenosine monophosphate (cAMP) can elicit distinct functional responses in cardiac myocytes. Selectively sequestering cAMP activity to discrete intracellular microdomains is considered essential for generating receptor-specific responses. The processes that control this aspect of compartmentalized cAMP signaling, however, are not completely clear. Over the years, technological innovations have provided critical breakthroughs in advancing our understanding of the mechanisms underlying cAMP compartmentation. Some of the factors identified include localized production of cAMP by differential distribution of receptors, localized breakdown of this second messenger by targeted distribution of phosphodiesterase enzymes, and limited diffusion of cAMP by protein kinase A (PKA)dependent buffering or physically restricted barriers. The aim of this review is to provide a discussion of our current knowledge and highlight some of the gaps that still exist in the field of cAMP compartmentation in cardiac myocytes.