Compartmentalized cAMP signaling in cardiac ventricular myocytes

• Published in: Cellular signalling 2022-01, Vol.89, p.110172-110172, Article 110172
• Main Authors: Agarwal, Shailesh R., Sherpa, Rinzhin T., Moshal, Karni S., Harvey, Robert D.
• Format: Article
• Language: English
• Subjects: beta-Adrenergic receptor; Buffering; cAMP compartmentation; Cardiac myocytes; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Heart Ventricles - metabolism; Myocytes, Cardiac - metabolism; Phosphodiesterase; Prostaglandin receptor; Protein kinase A; Restricted spaces; Signal Transduction - physiology
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2021.110172

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. •Localized production of cAMP by different GPCRs is often involved.•Localized degradation of cAMP by phosphodiesterases alone may not be sufficient.•Restricted diffusion of cAMP due buffering by protein kinase A is a likely factor.•Diffusion of cAMP limited by physical barriers may also contribute.•Multiple factors affecting cAMP compartmentation are altered by disease.