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Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions.

, , , and . Biophys. J. 84 (2 Pt 1): 897--909 (February 2003)

Abstract

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 (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.

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