Fellowship for Sarah Kosta: Dual Filament Regulation of Myocardial Power Output

Grants and Contracts Details


Myofilament deactivation in isotonic contractions During a heartbeat, cardiac action potentials induce transient increases in the intracellular calcium concentration. The calcium ions activate the actin thin filaments and allow for cross-bridges to attach to actin and generate active force. During blood ejection, myofilaments contract and shorten against a nearly constant arterial pressure. Thus, they undergo isotonic contractions. The velocity of shortening and the produced force in the isotonic phase dictate the myocardial power output. Little is known about the mechanisms that regulate isotonic contractions. In particular, a progressive slowing of shortening has been observed in single cells preparations at submaximal activation. This project aims to investigate this apparent contractile deactivation during loaded shortenings. This would lead to new insights in cardiac function at end systole, where calcium activation is dropping, and myofilaments deactivation must occur to anticipate the following diastole. The main purpose is to test the hypothesis of a faster cross-bridge detachment rate during shortening. This will be done using a computational model of a half-sarcomere contraction (Aim 1). This model will allow to evaluate the role of cross-bridge kinetics in deactivating the myofilaments during loaded shortenings. The second goal is to perform experiments on human myocardium. Isotonic contractions will be implemented, and muscle stiffness will be assessed (Aim 2). This stiffness measurement is an indication of the number of attached cross-bridges. We expect these experimental data to validate the conclusions drawn with the computational model. We will then have strong evidence to interpret the deactivation of myofilament at end systole.
Effective start/end date4/1/217/22/22


  • American Heart Association: $89,362.00


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