TY - JOUR
T1 - Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions
AU - Rice, John Jeremy
AU - Stolovitzky, Gustavo
AU - Tu, Yuhai
AU - De Tombet, Pieter P.
N1 - Funding Information:
This work was supported, in part, by National Institutes of Health Research Grants RO1-HL52322 and PO1-HL62426, Project 4 (P.P.T.). The National Aeronautics and Space Administration supported part of this work through NASA Cooperative Agreement NCC 9-58 with the National Space Biomedical Research Institute.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - We 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 (Ca50) 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 Ca50, and becomes uncooperative again at higher [Ca]. The steepness near Ca50 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 Ca50, 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.
AB - We 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 (Ca50) 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 Ca50, and becomes uncooperative again at higher [Ca]. The steepness near Ca50 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 Ca50, 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.
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U2 - 10.1016/S0006-3495(03)74907-8
DO - 10.1016/S0006-3495(03)74907-8
M3 - Article
C2 - 12547772
AN - SCOPUS:0037305919
SN - 0006-3495
VL - 84
SP - 897
EP - 909
JO - Biophysical journal
JF - Biophysical journal
IS - 2 I
ER -