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Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactionsWe have developed a model of cardiac thin filament activation using an Ising model approach from equilibrium statistical physics. This model explicitly represents nearest-neighbor interactions between 26 troponin/tropomyosin units along a one-dimensional array that represents the cardiac thin filament. With transition rates chosen to match experimental data, the results show that the resulting force-pCa (F-pCa) relations are similar to Hill functions with asymmetries, as seen in experimental data. Specifically, Hill plots showing (log(F/(1-F)) vs. log [Ca]) reveal a steeper slope below the half activation point (Ca(50)) compared with above. Parameter variation studies show interplay of parameters that affect the apparent cooperativity and asymmetry in the F-pCa relations. The model also predicts that Ca binding is uncooperative for low [Ca], becomes steeper near Ca(50), and becomes uncooperative again at higher [Ca]. The steepness near Ca(50) mirrors the steep F-pCa as a result of thermodynamic considerations. The model also predicts that the correlation between troponin/tropomyosin units along the one-dimensional array quickly decays at high and low [Ca], but near Ca(50), high correlation occurs across the whole array. This work provides a simple model that can account for the steepness and shape of F-pCa relations that other models fail to reproduce.
Document ID
20040087877
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Rice, John Jeremy
(IBM T. J. Watson Research Center Yorktown Heights, New York 10598, United States)
Stolovitzky, Gustavo
Tu, Yuhai
de Tombe, Pieter P.
Bers, D. M.
Date Acquired
August 21, 2013
Publication Date
February 1, 2003
Publication Information
Publication: Biophysical journal
Volume: 84
Issue: 2 Pt 1
ISSN: 0006-3495
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: R01-HL52322
CONTRACT_GRANT: P01-HL62426
Distribution Limits
Public
Copyright
Other
Keywords
Evaluation Studies
NASA Discipline Cardiopulmonary
Validation Studies
Non-NASA Center
NASA Program Biomedical Research and Countermeasures

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