A Stochastic Spatiotemporal Model of Rat Ventricular Myocyte Calcium Dynamics Demonstrated Necessary Features for Calcium Wave Propagation.
A Stochastic Spatiotemporal Model of Rat Ventricular Myocyte Calcium Dynamics Demonstrated Necessary Features for Calcium Wave Propagation.
复制标题
大鼠心室心肌钙动力学的随机时空模型证明了钙波传播的必要特征。
DOI：
10.3390/membranes11120989
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发表时间：
2021-12-18
期刊：
影响因子：
4.2
通讯作者：
Jafri MS
中科院分区：
文献类型：
--
作者：
Hoang-Trong TM;Ullah A;Lederer WJ;Jafri MS
钙（Ca2+）在心肌细胞的兴奋和收缩中起着核心作用。实验表明，钙释放是随机的，局部调控，提示细胞内钙水平可能存在空间异质性。这种空间异质性可能在调节不同的信号通路中很重要。在50多年的计算细胞生物学中，计算模型已经发展到包含更多的离子电流，从确定性模型到随机模型。而周期性的增加细胞质Ca2+浓度驱动心脏收缩，异常Ca2+释放可以潜在的心律失常。然而，由于使用三维随机计算模型的计算费用，对钙离子的空间作用的研究受到限制。在本文中，我们介绍了一个全细胞水平的大鼠心室肌细胞三维随机计算模型，该模型包含详细的钙动力学，包括(1)非均匀释放位点放置，(2)非均匀膜离子电流和膜缓冲，(3)随机钙泄漏动力学和(4)非连接或流氓ryanodine受体。该模型模拟了在闭细胞条件下钙超载条件下发生的火花诱导的火花激活和火花诱导的Ca2+波的起始和传播，而不是在Ca2+水平正常时。这被认为是重要的，因为Ca2+波的存在有助于心律失常电流的激活。
Calcium (Ca2+) plays a central role in the excitation and contraction of cardiac myocytes. Experiments have indicated that calcium release is stochastic and regulated locally suggesting the possibility of spatially heterogeneous calcium levels in the cells. This spatial heterogeneity might be important in mediating different signaling pathways. During more than 50 years of computational cell biology, the computational models have been advanced to incorporate more ionic currents, going from deterministic models to stochastic models. While periodic increases in cytoplasmic Ca2+ concentration drive cardiac contraction, aberrant Ca2+ release can underly cardiac arrhythmia. However, the study of the spatial role of calcium ions has been limited due to the computational expense of using a three-dimensional stochastic computational model. In this paper, we introduce a three-dimensional stochastic computational model for rat ventricular myocytes at the whole-cell level that incorporate detailed calcium dynamics, with (1) non-uniform release site placement, (2) non-uniform membrane ionic currents and membrane buffers, (3) stochastic calcium-leak dynamics and (4) non-junctional or rogue ryanodine receptors. The model simulates spark-induced spark activation and spark-induced Ca2+ wave initiation and propagation that occur under conditions of calcium overload at the closed-cell condition, but not when Ca2+ levels are normal. This is considered important since the presence of Ca2+ waves contribute to the activation of arrhythmogenic currents.
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DOI：
10.1016/j.biocel.2009.02.016
发表时间：
2009-10
影响因子：
4
作者：
Aon, M. A.;Cortassa, S.;Akar, F. G.;Brown, D. A.;Zhou, L.;O'Rourke, B.
通讯作者：
O'Rourke, B.
影响因子：
20.1
作者：
Brette, F;Orchard, CH
通讯作者：
Orchard, CH
影响因子：
3.4
作者：
Chen-Izu, Ye;McCulle, Stacey L.;Izu, Leighton T.
通讯作者：
Izu, Leighton T.
影响因子：
4.8
作者：
Greene, AL;Lalli, MJ;Periasamy, M
通讯作者：
Periasamy, M
影响因子：
56.9
作者：
CHENG, H;LEDERER, WJ;CANNELL, MB
通讯作者：
CANNELL, MB