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(Circulation Research. 1998;83:471-480.)
© 1998 American Heart Association, Inc.


Review

Troponin and Tropomyosin

Proteins That Switch on and Tune in the Activity of Cardiac Myofilaments

R. John Solaro, , Helen M. Rarick

From the Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago.

Correspondence to R. John Solaro, PhD, Department of Physiology and Biophysics (M/C 901), College of Medicine, University of Illinois at Chicago, 835 South Wolcott Ave, Chicago, IL 60612-7342.

Abstract—We present a current perception of the regulation of activation of cardiac myofilaments with emphasis on troponin (Tn) and tropomyosin (Tm). Activation involves both a Ca2+-regulated molecular switch and a potentiated state, dependent on feedback effects of force-generating crossbridges. Recent developments in the elucidation of the structure and arrangement of the myofilament proteins offer insights into the molecular interactions that constitute the switching and potentiating mechanisms. Transgenic mice overexpressing myofilament proteins, in vitro studies of mutant myofilament proteins, multidimensional multinuclear nuclear magnetic resonance, and fluorescence resonance energy transfer offer important approaches to understanding the molecular signaling processes. These studies reveal special features of the cardiac myofilament proteins that appear specialized for the unique functions of the heart. An important aspect of these special features is their role in mechanical, chemical, and neurohumoral coupling processes that tune myofilament activation to hemodynamics and beating frequency. Understanding these processes has become essential to understanding cardiac pathologies such as heart failure, ischemia and reperfusion injury, stunning, and familial hypertrophic cardiac myopathies.


Key Words: heart • thin filament • myosin • actin • Ca2+ binding protein




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J. H. Marden, G. H. Fitzhugh, M. R. Wolf, K. D. Arnold, and B. Rowan
From the Cover: Alternative splicing, muscle calcium sensitivity, and the modulation of dragonfly flight performance
PNAS, December 21, 1999; 96(26): 15304 - 15309.
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ANN INTERN MEDHome page
A. C. Fox and R. I. Levin
Ruptured Plaques and Leaking Cells: Cost-Effectiveness in the Diagnosis of Acute Coronary Syndromes
Ann Intern Med, December 21, 1999; 131(12): 968 - 970.
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Circ. Res.Home page
D. B. Foster and J. E. Van Eyk
In Search of the Proteins That Cause Myocardial Stunning
Circ. Res., September 3, 1999; 85(5): 470 - 472.
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J. Physiol.Home page
P. J Hanley, A. A Young, I. J LeGrice, S. G Edgar, and D. S Loiselle
3-Dimensional configuration of perimysial collagen fibres in rat cardiac muscle at resting and extended sarcomere lengths
J. Physiol., June 15, 1999; 517(3): 831 - 837.
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J. Biol. Chem.Home page
V. Gaponenko, E. Abusamhadneh, M. B. Abbott, N. Finley, G. Gasmi-Seabrook, R. J. Solaro, M. Rance, and P. R. Rosevear
Effects of Troponin I Phosphorylation on Conformational Exchange in the Regulatory Domain of Cardiac Troponin C
J. Biol. Chem., June 11, 1999; 274(24): 16681 - 16684.
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J. Physiol.Home page
R. C Fentzke, S. H Buck, J. R Patel, H. Lin, B. M Wolska, M. O Stojanovic, A. F Martin, R J. Solaro, R. L Moss, and J. M Leiden
Impaired cardiomyocyte relaxation and diastolic function in transgenic mice expressing slow skeletal troponin I in the heart
J. Physiol., May 15, 1999; 517(1): 143 - 157.
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Circ. Res.Home page
B. M. Wolska, R. S. Keller, C. C. Evans, K. A. Palmiter, R. M. Phillips, M. Muthuchamy, J. Oehlenschlager, D. F. Wieczorek, P. P. de Tombe, and R. J. Solaro
Correlation Between Myofilament Response to Ca2+ and Altered Dynamics of Contraction and Relaxation in Transgenic Cardiac Cells That Express ß-Tropomyosin
Circ. Res., April 16, 1999; 84(7): 745 - 751.
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Circ. Res.Home page
R. L. Moss
Plasticity in the Dynamics of Myocardial Contraction : Ca2+, Crossbridge Kinetics, or Molecular Cooperation
Circ. Res., April 16, 1999; 84(7): 862 - 865.
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Circ. Res.Home page
R. J. Solaro
Troponin I, Stunning, Hypertrophy, and Failure of the Heart
Circ. Res., January 22, 1999; 84(1): 122 - 124.
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J. Biol. Chem.Home page
J. R. Pearlstone, M. Chandra, M. M. Sorenson, and L. B. Smillie
Biological Function and Site II Ca2+-induced Opening of the Regulatory Domain of Skeletal Troponin C Are Impaired by Invariant Site I or II Glu Mutations
J. Biol. Chem., November 3, 2000; 275(45): 35106 - 35115.
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J. Biol. Chem.Home page
K. Elliott, H. Watkins, and C. S. Redwood
Altered Regulatory Properties of Human Cardiac Troponin I Mutants That Cause Hypertrophic Cardiomyopathy
J. Biol. Chem., July 14, 2000; 275(29): 22069 - 22074.
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J. Biol. Chem.Home page
X. Wang, M. X. Li, L. Spyracopoulos, N. Beier, M. Chandra, R. J. Solaro, and B. D. Sykes
Structure of the C-domain of Human Cardiac Troponin C in Complex with the Ca2+ Sensitizing Drug EMD 57033
J. Biol. Chem., June 29, 2001; 276(27): 25456 - 25466.
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J. Biol. Chem.Home page
M. B. Abbott, V. Gaponenko, E. Abusamhadneh, N. Finley, G. Li, A. Dvoretsky, M. Rance, R. J. Solaro, and P. R. Rosevear
Regulatory Domain Conformational Exchange and Linker Region Flexibility in Cardiac Troponin C Bound to Cardiac Troponin I
J. Biol. Chem., June 30, 2000; 275(27): 20610 - 20617.
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Circ. Res.Home page
S.-J. Kim, R. K. Kudej, A. Yatani, Y.-K. Kim, G. Takagi, R. Honda, D. A. Colantonio, J. E. Van Eyk, D. E. Vatner, R. L. Rasmusson, et al.
A Novel Mechanism for Myocardial Stunning Involving Impaired Ca2+ Handling
Circ. Res., October 26, 2001; 89(9): 831 - 837.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
B. M. Wolska, G. M. Arteaga, J. R. Pena, G. Nowak, R. M. Phillips, S. Sahai, P. P. de Tombe, A. F. Martin, E. G. Kranias, and R. J. Solaro
Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of {beta}-Adrenergic Stimulation
Circ. Res., May 3, 2002; 90(8): 882 - 888.
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