doi: 10.1161/01.RES.0000127125.61647.4F
© 2004 American Heart Association, Inc.
Reviews |
Myosin Crossbridge Activation of Cardiac Thin Filaments
Implications for Myocardial Function in Health and Disease
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
This article has been cited by other articles:
 |
|
 |
|
  Y. Ge, I. N. Rybakova, Q. Xu, and R. L. Moss Top-down high-resolution mass spectrometry of cardiac myosin binding protein C revealed that truncation alters protein phosphorylation state PNAS, August 4, 2009; 106(31): 12658 - 12663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Shaffer, R. W. Kensler, and S. P. Harris The Myosin-binding Protein C Motif Binds to F-actin in a Phosphorylation-sensitive Manner J. Biol. Chem., May 1, 2009; 284(18): 12318 - 12327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Solaro Maintaining cooperation among cardiac myofilament proteins through thick and thin J. Physiol., January 1, 2009; 587(1): 3 - 3. [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Tong, J. E. Stelzer, M. L. Greaser, P. A. Powers, and R. L. Moss Acceleration of Crossbridge Kinetics by Protein Kinase A Phosphorylation of Cardiac Myosin Binding Protein C Modulates Cardiac Function Circ. Res., October 24, 2008; 103(9): 974 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Colson, T. Bekyarova, M. R. Locher, D. P. Fitzsimons, T. C. Irving, and R. L. Moss Protein Kinase A-Mediated Phosphorylation of cMyBP-C Increases Proximity of Myosin Heads to Actin in Resting Myocardium Circ. Res., August 1, 2008; 103(3): 244 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Davis and S. B. Tikunova Ca2+ exchange with troponin C and cardiac muscle dynamics Cardiovasc Res, March 1, 2008; 77(4): 619 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cammarato, C. M. Dambacher, A. F. Knowles, W. A. Kronert, R. Bodmer, K. Ocorr, and S. I. Bernstein Myosin Transducer Mutations Differentially Affect Motor Function, Myofibril Structure, and the Performance of Skeletal and Cardiac Muscles Mol. Biol. Cell, February 1, 2008; 19(2): 553 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. de Tombe and G. J. M. Stienen Impact of temperature on cross-bridge cycling kinetics in rat myocardium J. Physiol., October 15, 2007; 584(2): 591 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Stelzer, J. R. Patel, J. W. Walker, and R. L. Moss Differential Roles of Cardiac Myosin-Binding Protein C and Cardiac Troponin I in the Myofibrillar Force Responses to Protein Kinase A Phosphorylation Circ. Res., August 31, 2007; 101(5): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Solaro Nitroxyl effects on myocardium provide new insights into the significance of altered myofilament response to calcium in the regulation of contractility J. Physiol., May 1, 2007; 580(3): 697 - 697. [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Hinken and R. J. Solaro A Dominant Role of Cardiac Molecular Motors in the Intrinsic Regulation of Ventricular Ejection and Relaxation Physiology, April 1, 2007; 22(2): 73 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Campbell and A. M. Holbrook The rate of tension recovery in cardiac muscle correlates with the relative residual tension prevailing after restretch Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H2020 - H2022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Engel, T. Kobayashi, B. Biesiadecki, J. Davis, S. Tikunova, S. Wu, and R. J. Solaro Identification of a Region of Troponin I Important in Signaling Cross-bridge-dependent Activation of Cardiac Myofilaments J. Biol. Chem., January 5, 2007; 282(1): 183 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Razumova, J. F. Shaffer, A.-Y. Tu, G. V. Flint, M. Regnier, and S. P. Harris Effects of the N-terminal Domains of Myosin Binding Protein-C in an in Vitro Motility Assay: EVIDENCE FOR LONG-LIVED CROSS-BRIDGES J. Biol. Chem., November 24, 2006; 281(47): 35846 - 35854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Stelzer, J. R. Patel, and R. L. Moss Acceleration of Stretch Activation in Murine Myocardium due to Phosphorylation of Myosin Regulatory Light Chain J. Gen. Physiol., August 28, 2006; 128(3): 261 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Moss and D. P. Fitzsimons Myosin Light Chain 2 Into the Mainstream of Cardiac Development and Contractility Circ. Res., August 4, 2006; 99(3): 225 - 227. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Stelzer, S. B. Dunning, and R. L. Moss Ablation of Cardiac Myosin-Binding Protein-C Accelerates Stretch Activation in Murine Skinned Myocardium Circ. Res., May 12, 2006; 98(9): 1212 - 1218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Campbell and M. Chandra Functions of Stretch Activation in Heart Muscle J. Gen. Physiol., January 30, 2006; 127(2): 89 - 94. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Stelzer, L. Larsson, D. P. Fitzsimons, and R. L. Moss Activation Dependence of Stretch Activation in Mouse Skinned Myocardium: Implications for Ventricular Function J. Gen. Physiol., January 30, 2006; 127(2): 95 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.J. Marian On Mice, Rabbits, and Human Heart Failure Circulation, May 10, 2005; 111(18): 2276 - 2279. [Full Text] [PDF]
|
|
|
|
|
|
M Kruger, S Zittrich, C Redwood, N Blaudeck, J James, J Robbins, G Pfitzer, and R Stehle Effects of the mutation R145G in human cardiac troponin I on the kinetics of the contraction-relaxation cycle in isolated cardiac myofibrils J. Physiol., April 15, 2005; 564(2): 347 - 357. [Abstract] [Full Text] [PDF]
|
|