ArticleThe Journal of general physiology2025
Modeling the effects of thin filament near-neighbor cooperative interactions in mammalian myocardium.
Article in The Journal of general physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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- Modeling cardiac contractile cooperativity across species.The Journal of general physiology · 2025Article
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Abstract
The mechanisms underlying cooperative activation and inactivation of myocardial force extend from local, near-neighbor interactions involving troponin-tropomyosin regulatory units (RU) and crossbridges (XB) to more global interactions across the sarcomere. To better understand these mechanisms in the hearts of small and large mammals, we undertook a simplified mathematical approach to assess the contribution of three types of near-neighbor cooperative interactions, i.e., RU-induced, RU-activation (RU-RU), crossbridge-induced, crossbridge-binding (XB-XB), and XB-induced, RU-activation (XB-RU). We measured the Ca2+ and activation dependence of the rate constant of force redevelopment in murine- and porcine-permeabilized ventricular myocardium. Mathematical modeling of these three near-neighbor interactions yielded nonlinear expressions for the RU-RU and XB-RU rate coefficients (kon and koff) and XB-XB rate coefficients describing the attachment of force-generating crossbridges (f and f'). The derivation of single cooperative coefficient parameters (u = RU-RU, w = XB-RU, and v = XB-XB) permitted an initial assessment of the strength of each near-neighbor interaction. The parameter sets describing the effects of discrete XB-XB or XB-RU interactions failed to adequately fit the in vitro contractility data in either murine or porcine myocardium. However, the Ca2+ dependence of ktr in murine and porcine ventricular myocardium was well fit by parameter sets incorporating the RU-RU cooperative interaction. Our results indicate that a significantly stronger RU-RU interaction is present in porcine ventricular myocardium compared with murine ventricular myocardium and that the relative strength of the near-neighbor RU-RU interaction contributes to species-specific myocardial contractile dynamics in small and large mammals.
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