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(Circulation Research. 2003;93:1170.)
© 2003 American Heart Association, Inc.

Reviews

Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins

Physiological and Pathological Implications

Steven B. Marston, Charles S. Redwood

From the Imperial College London (S.B.M.), National Heart and Lung Institute, London, UK, and Department of Cardiovascular Medicine (C.S.R.), University of Oxford, UK.

Correspondence to Steven B. Marston, Imperial College London, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK. E-mail S.Marston{at}imperial.ac.uk

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
Modulation of Thin Filament Activation by Crossbridges
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-Disks in Intracellular Signaling and Cardiac Function

R. John Solaro Guest Editor

In the heart, the contractile apparatus is adapted to the specific demands of the organ for continuous rhythmic contraction. The specialized contractile properties of heart muscle are attributable to the expression of cardiac-specific isoforms of contractile proteins. This review describes the isoforms of the thin filament proteins actin and tropomyosin and the three troponin subunits found in human heart muscle, how the isoform profiles of these proteins change during development and disease, and the possible functional consequences of these changes. During development of the heart, there is a distinctive switch of isoform expression at or shortly after birth; however, during adult life, thin filament protein isoform composition seems to be stable despite protein turnover rates of 3 to 10 days. The pattern of isoforms of actin, tropomyosin, troponin I, troponin C, and troponin T is not affected by aging or heart disease (ischemia and dilated cardiomyopathy). The evidence for proteolysis of thin filament proteins in situ during ischemia and stunning is evaluated, and it is concluded that C-terminal cleavage of troponin I is a feature of irreversibly injured myocardium but may not play a role in reversible stunning.

Key Words: actin • troponin • tropomyosin • calpain • stunning

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