A Computational Study of the Effects of Tachycardia-Induced Remodeling on Calcium Wave Propagation in Rabbit Atrial Myocytes.
A Computational Study of the Effects of Tachycardia-Induced Remodeling on Calcium Wave Propagation in Rabbit Atrial Myocytes.
复制标题
DOI：
10.3389/fphys.2021.651428
复制
发表时间：
2021
影响因子：
4
通讯作者：
Sundnes J
中科院分区：
文献类型：
--
作者：
Vagos MR;Arevalo H;Heijman J;Schotten U;Sundnes J
在没有发育良好的T-小管系统的心房心肌细胞中，钙从外周向中心扩散，产生向心波模式。在心房颤动期间，心房肌细胞的快速激活诱导扩散性质的复杂重构，导致钙不能以完全再生的方式向中心传播;这种现象称为“钙沉默”。这已经在暴露于长时间快速起搏后的兔心房肌细胞中观察到。尽管实验研究已经指出了钙沉默的可能机制，但它们的个体效应和相对重要性在很大程度上仍然未知。在这项研究中，我们使用兔心房心肌细胞的计算建模查询的个人和综合影响的机制，导致钙沉默和异常钙波传播。我们采用了一个人口的模型，从一个新开发的模型，兔心房肌细胞的细胞内钙处理的空间表示。我们在模型中选择了代表实验观察到的与钙沉默有关的细胞重塑的参数，并在群体中缩放其值以匹配实验观察结果。特别地，我们改变了ICaL、INCX和INaK的最大电导、RyR开放概率、RyR密度、Serca 2a密度和钙缓冲强度。我们通过独立改变参数将重塑纳入16个模型的人群中，这些参数重现了实验观察到的细胞重塑，并量化了钙动力学和波传播模式的变化。结果显示ICaL在驱动钙沉默中的强烈作用，INCX、INaK和RyR密度在一些模型中也导致钙沉默。在INCX和Serca 2a密度已改变的一些模型中观察到交替钙。同时纳入所有重塑参数的变化导致所有模型中的钙沉默，表明降低ICaL在群体表型中的主要作用。
In atrial cardiomyocytes without a well-developed T-tubule system, calcium diffuses from the periphery toward the center creating a centripetal wave pattern. During atrial fibrillation, rapid activation of atrial myocytes induces complex remodeling in diffusion properties that result in failure of calcium to propagate in a fully regenerative manner toward the center; a phenomenon termed “calcium silencing.” This has been observed in rabbit atrial myocytes after exposure to prolonged rapid pacing. Although experimental studies have pointed to possible mechanisms underlying calcium silencing, their individual effects and relative importance remain largely unknown. In this study we used computational modeling of the rabbit atrial cardiomyocyte to query the individual and combined effects of the proposed mechanisms leading to calcium silencing and abnormal calcium wave propagation. We employed a population of models obtained from a newly developed model of the rabbit atrial myocyte with spatial representation of intracellular calcium handling. We selected parameters in the model that represent experimentally observed cellular remodeling which have been implicated in calcium silencing, and scaled their values in the population to match experimental observations. In particular, we changed the maximum conductances of ICaL, INCX, and INaK, RyR open probability, RyR density, Serca2a density, and calcium buffering strength. We incorporated remodeling in a population of 16 models by independently varying parameters that reproduce experimentally observed cellular remodeling, and quantified the resulting alterations in calcium dynamics and wave propagation patterns. The results show a strong effect of ICaL in driving calcium silencing, with INCX, INaK, and RyR density also resulting in calcium silencing in some models. Calcium alternans was observed in some models where INCX and Serca2a density had been changed. Simultaneously incorporating changes in all remodeled parameters resulted in calcium silencing in all models, indicating the predominant role of decreasing ICaL in the population phenotype.
登录
查看更多内容
DOI：
10.1016/j.bbamcr.2011.01.030
发表时间：
2011-05-01
影响因子：
5.1
作者：
Bootman, Martin D.;Smyrnias, Ioannis;Roderick, H. Llewelyn
通讯作者：
Roderick, H. Llewelyn
DOI：
10.1085/jgp.117.2.119
发表时间：
2001-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Weber CR;Ginsburg KS;Philipson KD;Shannon TR;Bers DM
通讯作者：
Bers DM
影响因子：
3.4
作者：
Xie, Yuanfang;Izu, Leighton T.;Sato, Daisuke
通讯作者：
Sato, Daisuke
影响因子：
10.8
作者：
Workman, AJ;Kane, AK;Rankin, AC
通讯作者：
Rankin, AC
影响因子：
37.8
作者：
Smith, Godfrey L.;Eisner, David A.
通讯作者：
Eisner, David A.