Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.
Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.
复制标题
DOI：
10.3389/fphys.2022.836622
复制
发表时间：
2022
影响因子：
4
通讯作者：
Heijman J
中科院分区：
文献类型：
--
作者：
Colman MA;Alvarez-Lacalle E;Echebarria B;Sato D;Sutanto H;Heijman J
细胞内钙的调节是心脏电生理和兴奋-收缩偶联的关键组成部分。钙火花，细胞内钙瞬变的基本元素，是在专门的纳米结构域，共同定位的兰尼碱受体和L-型钙通道。然而，钙稳态最终在细胞尺度上通过空间分离但扩散偶联的纳米结构域与具有强非线性相互作用的其他亚细胞和表面膜钙转运通道的相互作用来调节;并且心脏电生理学和心律失常机制最终是组织尺度现象，由偶联的肌细胞的异质群体的相互作用来调节。成像模式和图像分析的最新进展使得能够超分辨率重建负责调节钙稳态的结构，包括纳米结构域本身的内部结构。将功能和成像数据从纳米结构域外推到整个心脏是不平凡的，但对于深入了解疾病机制至关重要。计算建模在将亚细胞尺度的结构和功能数据相关联以及跨尺度转换数据方面发挥着重要作用。这篇综述涵盖了最近的方法学进展，使基于图像的建模的单个nanodomain和整个心肌细胞，以及多尺度模拟方法的发展，以整合数据从纳米到整个心脏。首先，方法来克服模拟空间钙动力学的纳米领域的计算挑战进行了讨论，包括在这个规模的基于图像的建模。然后，最近的全细胞模型，能够捕获一系列不同的结构（如T-系统和线粒体）和细胞的异质性/变异性进行了讨论，在两个不同层次的离散化。然后讨论了在组织尺度模型中整合模型和数据并模拟随机动力学的新方法，从而阐明了纳米结构域重塑导致心律失常和收缩功能障碍的机制。模型的差异和未来的发展方向的观点提供了整个。
Regulation of intracellular calcium is a critical component of cardiac electrophysiology and excitation-contraction coupling. The calcium spark, the fundamental element of the intracellular calcium transient, is initiated in specialized nanodomains which co-locate the ryanodine receptors and L-type calcium channels. However, calcium homeostasis is ultimately regulated at the cellular scale, by the interaction of spatially separated but diffusively coupled nanodomains with other sub-cellular and surface-membrane calcium transport channels with strong non-linear interactions; and cardiac electrophysiology and arrhythmia mechanisms are ultimately tissue-scale phenomena, regulated by the interaction of a heterogeneous population of coupled myocytes. Recent advances in imaging modalities and image-analysis are enabling the super-resolution reconstruction of the structures responsible for regulating calcium homeostasis, including the internal structure of nanodomains themselves. Extrapolating functional and imaging data from the nanodomain to the whole-heart is non-trivial, yet essential for translational insight into disease mechanisms. Computational modeling has important roles to play in relating structural and functional data at the sub-cellular scale and translating data across the scales. This review covers recent methodological advances that enable image-based modeling of the single nanodomain and whole cardiomyocyte, as well as the development of multi-scale simulation approaches to integrate data from nanometer to whole-heart. Firstly, methods to overcome the computational challenges of simulating spatial calcium dynamics in the nanodomain are discussed, including image-based modeling at this scale. Then, recent whole-cell models, capable of capturing a range of different structures (such as the T-system and mitochondria) and cellular heterogeneity/variability are discussed at two different levels of discretization. Novel methods to integrate the models and data across the scales and simulate stochastic dynamics in tissue-scale models are then discussed, enabling elucidation of the mechanisms by which nanodomain remodeling underlies arrhythmia and contractile dysfunction. Perspectives on model differences and future directions are provided throughout.
登录
查看更多内容
心房颤动引起的电重塑的致心律失常效应：来自三维虚拟人体心房的见解
DOI：
10.1113/jphysiol.2013.254987
发表时间：
2013-09-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Colman MA;Aslanidi OV;Kharche S;Boyett MR;Garratt C;Hancox JC;Zhang H
通讯作者：
Zhang H
影响因子：
4
作者：
Kekenes-Huskey PM;Cheng Y;Hake JE;Sachse FB;Bridge JH;Holst MJ;McCammon JA;McCulloch AD;Michailova AP
通讯作者：
Michailova AP
影响因子：
4
作者：
Colman MA;Perez Alday EA;Holden AV;Benson AP
通讯作者：
Benson AP
影响因子：
4
作者：
Vagos MR;Arevalo H;Heijman J;Schotten U;Sundnes J
通讯作者：
Sundnes J
影响因子：
5
作者：
Brette, F;Despa, S;Orchard, CH
通讯作者：
Orchard, CH