Coupling of adjacent tropomyosins enhances cross-bridge-mediated cooperative activation in a markov model of the cardiac thin filament.

ABSTRACT: We developed a Markov model of cardiac thin filament activation that accounts for interactions among nearest-neighbor regulatory units (RUs) in a spatially explicit manner. Interactions were assumed to arise from structural coupling of adjacent tropomyosins (Tms), such that Tm shifting within each RU was influenced by the Tm status of its neighbors. Simulations using the model demonstrate that this coupling is sufficient to produce observed cooperativity in both steady-state and dynamic force-Ca(2+) relationships. The model was further validated by comparison with reported responses under various conditions including inhibition of myosin binding and the addition of strong-binding, non-force-producing myosin fragments. The model also reproduced the effects of 2.5 mM added P(i) on Ca(2+)-act

SUBMITTER: Campbell SG 

PROVIDER: S-EPMC2872217 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature