© 2000 American Heart Association, Inc.
Editorials |
Myosin Binding Protein C, a Potential Regulator of Cardiac Contractility
From Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia.
Correspondence to Saul Winegrad, Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085. E-mail BSG@Mail.Med.Upenn.Edu
Key Words: myosin binding protein C • myosin • cardiac contractility • cardiac muscle • cardiac regulation
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Introduction |
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The role of myosin binding protein C (MyBP-C) in the formation and function of striated muscle is unclear, even though the demonstration of its presence in the thick filaments of striated muscle was made by Offer et al1 more than 25 years ago.2 Because of the inability of myosin to form normal thick filaments in the absence of MyBP-C and the temporal correlation between the appearance of MyBP-C, thick filaments, and sarcomeres in developing striated muscle,3 4 5 MyBP-C is assumed to be essential for the formation and normal structure of thick filaments. The cardiac isoform of MyBP-C has an additional feature that is absent from the skeletal isoforms. There are 3 phosphorylation sites located in the cardiac motif portion of the molecule in the N-terminal region.6 In addition to these phosphorylatable sites, a Ca2+/calmodulin-regulated kinase specific for cardiac MyBP-C is bound to the thick filament.7 8 The combination of these features suggests that the function of MyBP-C in cardiac muscle can be modified posttranslationally by phosphorylation. Such a phosphorylation could be an important regulator of cardiac contractility. At least 5 transmitter-based mechanisms for the regulation of cardiac contractility are associated with changes in the degree of phosphorylation of MyBP-C: increased or decreased phosphorylation with increased or decreased contractility.
MyBP-C is located in a series of 7 to 9 sites, each separated by 43 nm
in the C zone of the sarcomere and most likely oriented perpendicular
to the axis of the filament.9 Within the C zone, there are
approximately 9 crossbridges
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