Membrane Microdomains and cAMP Compartmentation in Cardiac Myocytes

  • Shailesh R. Agarwal
  • Rennolds S. Ostrom
  • Robert D. Harvey
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol.)


Signaling through the diffusible second messenger, 3′,5′-cyclic adenosine monophosphate (cAMP) is critical to the regulation of cardiac function. Several different G-protein-coupled receptors, including β-adrenergic receptors, muscarinic receptors, and E-type prostaglandin receptors, elicit distinct responses using this ubiquitous second messenger. One critical paradigm that has emerged to explain this behavior is that cAMP signaling is compartmentalized. Spatially confining specific receptors and their downstream effector proteins to form subcellular signaling complexes has been proposed to allow for the high efficiency and fidelity in producing specific functional responses. In cardiac myocytes, lipid rafts created by cholesterol- and sphingolipid-rich membrane microdomains have been demonstrated to act as one means of sorting appropriate receptors and corresponding effectors to relevant subcellular locations. Caveolae, which represent a specific subset of lipid rafts, can dynamically attract or exclude specific signaling proteins through a variety of mechanisms to create highly localized and self-sufficient multi-molecular signaling complexes. Furthermore, disruption of this organization in disease states such as heart failure has been found to alter cAMP responses. In this review, we summarize the current understanding of the role of membrane domains in cAMP signaling in cardiac myocytes. We also highlight the insights gained from previous studies to offer new avenues of research in this expanding field of study.


Caveolae Lipid rafts Cardiac myocytes G-protein-coupled receptors Compartmentation Cyclic adenosine monophosphate 



Adenylyl cyclase




A-kinase-anchoring protein


3′,5′-Cyclic adenosine monophosphate


Caveolin 3


Caveolin scaffolding domain


Detergent-resistant membrane




Endothelial nitric oxide synthase


Exchange protein directly activated by cAMP


E-type prostaglandin receptor


G-protein-coupled receptor




M2 muscarinic receptor




Nitric oxide




Protein kinase A




Scanning ion conductance microscopy


Sarcoplasmic reticulum

T tubule

Transverse tubule


β1-Adrenergic receptor


β2-Adrenergic receptor



This work was supported by the National Institutes of Health grants GM101928 and GM107094.

Compliance with Ethical Standards

Conflict of Interest Statement

The authors declare that they have no conflict of interest.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Shailesh R. Agarwal
    • 1
  • Rennolds S. Ostrom
    • 2
  • Robert D. Harvey
    • 1
  1. 1.Department of PharmacologyUniversity of Nevada School of MedicineRenoUSA
  2. 2.Department of Biomedical and Pharmaceutical SciencesChapman University School of PharmacyIrvineUSA

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