Article,
Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions.
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.
Tags
- animals;
- binding;
- biological;
- calcium;
- cardiac
- comparative
- computer
- contraction;
- gov't,
- macromolecular
- mechanical;
- microfilaments;
- models,
- molecular
- motors;
- myocardial
- myocardium;
- myocy;
- myofibrils;
- non-p.h.s.;
- p.h.s.;
- protein
- rats;
- research
- simulation;
- stress,
- study;
- substances;
- support,
- tes,
- tropomyosin;
- troponin;
- u.s.
