Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions
Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions
复制标题
DOI：
10.1016/s0006-3495(03)74907-8
复制
发表时间：
2003-02-01
影响因子：
3.4
通讯作者：
de Tombe, PP
中科院分区：
文献类型：
--
作者：
Rice, JJ;Stolovitzky, G;de Tombe, PP
我们已经开发了一个模型的心脏细丝激活使用伊辛模型的方法从平衡统计物理。该模型明确表示最近邻相互作用之间的26肌钙蛋白/原肌球蛋白单位沿着一维阵列，代表心脏细丝。与过渡率选择匹配的实验数据，结果表明，由此产生的力-pCa（F-pCa）的关系是类似的希尔函数的不对称性，在实验数据中看到的。具体而言，显示（log（F/（1-F））vs. log [Ca]）的Hill图显示与上述相比，在半激活点（Ca-50）以下的斜率更陡。参数变化的研究表明，影响表观协同性和不对称性的F-pCa关系的参数的相互作用。该模型还预测，钙结合是不合作的低[Ca]，变得陡峭的Ca-50附近，并再次成为不合作的高[Ca]。Ca-50附近的陡度反映了由于热力学考虑而导致的陡峭的F-pCa。该模型还预测，肌钙蛋白/原肌球蛋白单元之间的相关性沿着一维阵列迅速衰减在高和低[Ca]，但在Ca-50附近，高相关性发生在整个阵列。这项工作提供了一个简单的模型，可以解释其他模型无法重现的F-pCa关系的陡峭度和形状。
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.