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(Circulation Research. 2004;94:1290.)
© 2004 American Heart Association, Inc.

Reviews

Myosin Crossbridge Activation of Cardiac Thin Filaments

Implications for Myocardial Function in Health and Disease

Richard L. Moss, Maria Razumova, Daniel P. Fitzsimons

From the Department of Physiology, University of Wisconsin Medical School, Madison, Wis.

Correspondence to Dr Richard L. Moss, Department of Physiology, 1300 University Ave, Madison, WI 53706. E-mail rlmoss{at}physiology.wisc.edu

This Review is part of a thematic series on Regulatory Signaling by Thin Filament Modulation, which includes the  following articles:

Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins: Physiological and Pathological Implications

Covalent and Noncovalent Modification of Thin Filament Action: The Essential Role of Troponin in Cardiac Muscle Regulation

At the Crossroads of Myocardial Signaling: The Role of Z-Discs in Intracellular Signaling and Cardiac Function

Myosin Crossbridge Activation of Cardiac Thin Filaments: Implications for Myocardial Function in Health and Disease
R. John Solaro Guest Editor

At the level of the myofibrillar proteins, activation of myocardial contraction is thought to involve switch-like regulation of crossbridge binding to the thin filaments. A central feature of this view of regulation is that Ca²⁺ binding to the low-affinity (3 µmol/L) site on troponin C alters the interactions of proteins in the thin filament regulatory strand, which leads to movement of tropomyosin from its blocking position on the thin filament and binding of crossbridges to actin. Although Ca²⁺ binding is a critical step in initiating contraction, this event alone does not account for the activation dependence of contractile properties of myocardium. Instead, activation is a highly cooperative process in which initial crossbridge binding to the thin filaments recruits additional crossbridge binding to actin as well as increased Ca²⁺ binding to troponin C. This review addresses possible roles of thin filament cooperativity in myocardium as a process that modulates the activation dependence of force and the rate of force development and also possible mechanisms by which cooperative signals are transmitted along the thick filament. Emerging evidence suggests that such mechanisms could contribute to the regulation of fundamental mechanical properties of myocardium and alterations in regulation that underlie contractile disorders in diseases such as cardiomyopathies.

Key Words: Ca²⁺ regulation • cardiac contractility • cardiomyopathy • cooperativity

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