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Brown Bag Lunch Series
July 27, 2021 @ 12:30 pm - 1:30 pm PDT
Presenter: Dan Fitzsimons is an Assistant Professor in the Department of Animal, Veterinary and Food Sciences at the University of Idaho. His research program focuses on the molecular mechanisms underlying contraction and relaxation in the healthy and diseased human heart.
Title: Molecular cooperativity and force development in human ventricular myocardium
In healthy mammalian myocardium, Ca2+ binding to troponin C (TnC) triggers a series of events that ultimately allows for the strong-binding of myosin cross-bridges to actin and the subsequent development of force. While Ca2+ binding to TnC initiates contraction, maximal activation of force and the kinetics of force development results from the synergistic activating effects of Ca2+ binding to TnC and binding of myosin to actin. Contraction (i.e., force development) is a cooperative process, involving activation of a given segment of the thin filament by Ca2+ and/or strong-binding cross-bridges which subsequently influences the activation of adjacent regions of the thin filament via near-neighbor interactions. To date, the cooperative activation of force and the kinetics of force development have been well characterized in rodent (i.e., mouse and rat) myocardium. However, the relative contributions of Ca2+ and strong-binding myosin cross-bridges to modulate contraction in human myocardium remain unexamined and unresolved.
The etiology of altered cooperativity in diseased human hearts is poorly understood since the fundamental molecular mechanisms underlying cooperativity in the healthy human heart have yet to be elucidated. Therefore, it is essential to fill the knowledge gap regarding the molecular mechanisms modulating contractility in the healthy human heart. These data will provide an essential foundation for future studies of altered myocardial function in both acquired and inherited cardiomyopathies.