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REVIEW

G-Protein Coupled Receptor Signaling in Myocardium: Not for the Faint of Heart

Misuk Kang, Ka Young Chung and Jeffery W. Walker

Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin

Catecholamines, endothelin-1 and angiotensin II are among a diverse group of diffusible extracellular signals that regulate pump function of the heart by binding to G-protein coupled receptors (GPCR). When the body demands a temporary boost of power output or if temporary budgeting of resources is required, these signals can adjust heart rate and contractile strength to maintain continuous perfusion of all vascular beds with nutrient- and oxygen-rich blood. Given adequate time in the face of prolonged challenges, activation of GPCRs can also promote "remodeling of the heart" by increasing cell size, organ size, and chamber dimensions, or by varying tissue composition and altering the expression of protein isoforms controlling excitability and contractility. A common feature of heart disease is the state of chronic activation of GPCR signaling systems. Paradoxically, whereas acute activation is beneficial, chronic activation often contributes to further deterioration of cardiac performance. A better understanding of how chronic GPCR activation contributes to the development of heart disease is needed so that it can be translated into better prevention and therapeutic strategies in the clinic.