Subcellular Targeting of PDE4 in Cardiac Myocytes and Generation of Signaling Compartments

Chapter
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol.)

Abstract

Of the 11 families of phosphodiesterases found in the human genome, three decades of pharmacological data have clearly implicated PDE3 in cardiac function. Conversely, much less was known about the PDE4 family of proteins expression and function in the heart. Indeed, PDE4-selective inhibitors were developed with the rationale that they would retain the beneficial properties of a nonselective inhibitor but would be devoid of cardiac effects. Yet in the last decade, a large body of work has been published on the expression and function of PDE4s in the hearts of humans and other mammals. To date, at least seven different PDE4 proteins encoded in the four PDE4 genes have been detected in cardiac cells. These PDE4s are targeted to different subcellular compartments of cardiac myocytes through interaction with several classes of scaffold proteins. This PDE4 sequestration in macromolecular complexes limits their access to cAMP in confined subcellular domains including the dyad, the sarcoplasmic reticulum, and the sarcomere. This molecular organization defines the distinctive role of the different PDE4 proteins in the different aspects of excitation/contraction coupling. In this chapter, the molecular properties and function of PDE4s in the different compartments of the cardiac myocytes will be reviewed.

Notes

Compliance with Ethical Standards

Conflict of Interest Statement

The author declares no conflict of interest.

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of ObstetricsUniversity of California, San FranciscoSan FranciscoUSA

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