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(Circulation Research. 2007;101:746.)
© 2007 American Heart Association, Inc.

Editorials

Regulation of Ryanodine Receptors in the Heart

Stephan Lehnart, Andrew R. Marks

From the Clyde and Helen Wu Center for Molecular Cardiology, Departments of Physiology and Cellular Biophysics (S.E.L., A.R.M.) and Medicine (A.R.M.), College of Physicians and Surgeons of Columbia University, New York.

Correspondence to Andrew R. Marks, the Clyde and Helen Wu Center for Molecular Cardiology, Departments of Physiology and Cellular Biophysics and Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032. E-mail arm42@columbia.edu

See related article, pages 819–829

Key Words: ryanodine • contractility • calcium • beta-receptor • heart

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
In response to exercise or other stresses, catecholamines are released into the circulation and within the heart. Catecholaminergic stimulation of ß1-adrenergic receptors (ß1ARs) in the heart increases heart rate (chronotropy) and contractility (inotropy), resulting in increased cardiac output during acute stress. Concurrent stimulation of ß2-ARs dilates blood vessels, which increase blood flow to exercising muscles, thereby matching increased cardiac output to metabolic demands of the organs.

The inotropic mechanisms investigated by Valdivia and colleagues¹ in the current issue of Circulation Research are essential for the acute stress-dependent increase of cardiac output. Each of the millions of muscle cells in the heart (cardiomyocytes) contribute to myocardial force development. Cardiomyocyte contraction is controlled by intracellular Ca²⁺ release through a process called excitation-contraction coupling (ECC) that involves the following steps: (1) an action potential (AP) depolarizes the cell membrane; (2) voltage-dependent plasma membrane L-type calcium channels (Ca_v1.2) opening results in a whole-cell inward Ca²⁺ current (I_Ca); (3) I_Ca activates cardiac ryanodine receptor (RyR2)/Ca²⁺ release channels located on the junctional sarcoplasmic reticulum (jSR), a process referred to as Ca²⁺-induced Ca²⁺ release (CICR); (4) Ca²⁺ binds to troponin C (TnC) leading to cross-bridge formation between myosin and actin and contraction of the sarcomere. Cardiomyocyte relaxation is signaled by a return of intracellular [Ca²⁺] to resting levels attributable to the following major mechanisms: (1) Ca_v1.2 inactivation; (2) RyR2 inactivation; (3) Ca²⁺ reuptake into the SR by SERCA2a pumps; and (4) Na⁺/Ca²⁺ exchange extrusion of Ca²⁺ to the extracellular space. . . . [Full Text of this Article]

Related Article:

Intact ß-Adrenergic Response and Unmodified Progression Toward Heart Failure in Mice With Genetic Ablation of a Major Protein Kinase A Phosphorylation Site in the Cardiac Ryanodine Receptor

Nancy A. Benkusky, Craig S. Weber, Joseph A. Scherman, Emily F. Farrell, Timothy A. Hacker, Manorama C. John, Patricia A. Powers, and Héctor H. Valdivia
Circ. Res. 2007 101: 819-829. [Abstract] [Full Text] [PDF]

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