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(Circulation. 2005;111:2276-2279.)
© 2005 American Heart Association, Inc.

Editorial

On Mice, Rabbits, and Human Heart Failure

A.J. Marian, MD

From the Section of Cardiology, Baylor College of Medicine, Houston, Tex.

Reprint requests to A. J. Marian, MD, Baylor College of Medicine, One Baylor Plaza, 519D, Houston, TX 77030. E-mail amarian@bcm.tmc.edu

Key Words: Editorials • heart failure • myosin isoforms • troponins • genetics

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

Sarcomeres, bundled into thick and thin filaments, are the units of contraction in the striated muscle. The thick filaments comprise several hundred hexameric myosin molecules, composed of 2 myosin heavy chain (MyHC) proteins, the molecular motor of contraction, and 2 regulatory and 2 essential light chains. The globular head of MyHC contains the binding domains for cardiac -actin and adenosine triphosphate (ATP) and is attached to a hinge region, which when flexed, moves the globular head over the thin filaments. The thin filaments comprise the cardiac troponin C (cTnC), T (cTnT), and I (cTnI) complex, -tropomyosin dimers, and cardiac -actin, maintained in a tight 1:1:7 stoichiometry. Several additional sarcomeric proteins, such as myosin-binding protein C, titin, obscurin, and telethonin contribute to the stabilization and function of the sarcomeres.

See pp 2330 and 2339

The troponin-tropomyosin complex regulates the calcium-dependent displacement of the thin filaments by the globular head of MyHC, which results in sarcomere shortening and generation of the force of muscle contraction.^1–3 Depolarization of membrane potential opens the L-type calcium channels and allows Ca²⁺ influx, which triggers calcium-induced calcium release by opening the ryanodine receptors in the junctional sarcoplasmic reticulum (SR). The cytosolic Ca²⁺ binds to cTnC at the low-affinity site and induces conformational changes, which lead to removal of the inhibitory domain of cTnI away from the -tropomyosin-actin complex (Figure).³ Consequently, MyHC binds to actin, hydrolyzes ATP to adenosine diphosphate (ADP) and inorganic phosphate, and displaces the actin filament. Each single myosin generates 3 to 4 . . . [Full Text of this Article]

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