心脏中的细胞内钙(Ca)循环在兴奋-收缩耦合和心律失常发生中起关键作用。在心肌细胞中,Ca释放通道,即,ryanodine受体(RyRs),聚集在肌浆网膜中,形成Ca释放单位(CRU)。CRU中的RyR集体起作用,引起离散的Ca释放事件,叫做Ca火花。一个细胞包含数百到数千个CRU,通过Ca扩散耦合形成CRU网络。在心肌细胞中观察到丰富的时空Ca动力学谱,包括Ca火花,火花簇,迷你波浪,持续的全细胞波,和振荡。已经开发了不同时间和空间尺度的模型来研究这些动态。由于CRU网络和时空Ca动力学的复杂性,对心脏系统中的钙循环动力学进行建模是具有挑战性的,特别是在纸巾销售方面。在这篇文章中,我们回顾了从单个RyRs到组织尺度的心脏系统Ca循环建模的进展,当前模型和不同建模方法的利弊,以及未来要解决的挑战。
Intracellular calcium (Ca) cycling in the heart plays key roles in excitation-contraction coupling and arrhythmogenesis. In cardiac myocytes, the Ca release channels, i.e., the ryanodine receptors (RyRs), are clustered in the sarcoplasmic reticulum membrane, forming Ca release units (CRUs). The RyRs in a CRU act collectively to give rise to discrete Ca release events, called Ca sparks. A cell contains hundreds to thousands of CRUs, diffusively coupled via Ca to form a CRU network. A rich spectrum of spatiotemporal Ca dynamics is observed in cardiac myocytes, including Ca sparks, spark clusters, mini-waves, persistent whole-cell waves, and oscillations. Models of different temporal and spatial scales have been developed to investigate these dynamics. Due to the complexities of the CRU network and the spatiotemporal Ca dynamics, it is challenging to model the Ca cycling dynamics in the cardiac system, particularly at the tissue sales. In this article, we review the progress of modeling of Ca cycling in cardiac systems from single RyRs to the tissue scale, the pros and cons of the current models and different modeling approaches, and the challenges to be tackled in the future.