title: Myosin crossbridge activation of cardiac thin filaments: implications for myocardial function in health and disease.
abstract: 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 (approximately 3 micromol/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.
authors.affiliation: Department of Physiology, University of Wisconsin Medical School, Madison, Wis, USA. rlmoss@physiology.wisc.edu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Moss
authors.forename: Maria
authors.initials: M
authors.lastname: Razumova
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Fitzsimons
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D007700:Kinetics; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D051381:Rats
chemical_list: D009218:Myosins; D002118:Calcium