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(Circulation Research. 2006;98:165.)
© 2006 American Heart Association, Inc.

Editorials

"Ryanogate"

Who Leaked the Calcium?

Sheldon E. Litwin

From the Division of Cardiology, the University of Utah and the Salt Lake City Veterans Affairs Medical Center, Salt Lake City.

Correspondence to Sheldon E. Litwin, MD, The University of Utah, Cardiology Division, 4A100 SOM, 30 N 1900 E, Salt Lake City, UT 84132. E-mail Sheldon.Litwin@hsc.utah.edu

See related article, pages 235–244

Key Words: CaMKII • calcium • sarcoplasmic reticulum • heart failure • action potential • ryanodine

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

The sarcoplasmic reticulum (SR) is the major intracellular calcium storage depot in cardiac muscle. Cycling of calcium between the lumen of the SR and the myoplasmic space occurs repetitively during each heart beat. Excitation–contraction coupling in the heart begins when calcium entry through voltage-gated L-type calcium channels in the sarcolemma induces the opening of calcium release channels (also known as ryanodine receptors, or RyR) in the adjacent SR. The majority of the calcium that enters the cytosol during the early portion of each cycle is then resequestered into the SR lumen via the actions of the calcium uptake protein, (sarco)endoplasmic reticulum calcium adenosine triphosphatase (SERCA). Tight regulation of the timing and quantity of these intracellular calcium fluxes is critical to achieve graded contractility and relaxation of the heart muscle. Such control allows optimal matching of cardiac function to heart rate and metabolic needs of the body. The mechanisms of excitation–contraction coupling have been reviewed more thoroughly elsewhere.¹

There has been a great deal of interest in the possibility that altered calcium homeostasis in the cardiac myocyte is the fundamental abnormality in the failing heart.² The most widely accepted hypothesis to explain myocyte dysfunction is that reduced abundance or activity of SERCA protein directly results in a lower rate of calcium uptake by the SR. In this scenario, reduced SR uptake results in lower SR calcium content, which then produces lower SR calcium release and reduced contractility. However, the "SERCA-centric" view of heart failure is at best only a partial explanation . . . [Full Text of this Article]

Related Article:

Increased Sarcoplasmic Reticulum Calcium Leak but Unaltered Contractility by Acute CaMKII Overexpression in Isolated Rabbit Cardiac Myocytes

Michael Kohlhaas, Tong Zhang, Tim Seidler, Darya Zibrova, Nataliya Dybkova, Astrid Steen, Stefan Wagner, Lu Chen, Joan Heller Brown, Donald M. Bers, and Lars S. Maier
Circ. Res. 2006 98: 235-244. [Abstract] [Full Text] [PDF]