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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.
AbstractWe 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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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. [Abstract] [Full Text] [PDF] |
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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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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. [Abstract] [Full Text] [PDF] |
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