Calcium (Ca²⁺) plays a central role in cardiomyocyte excitation-contraction coupling. To ensure an optimal electrical impulse propagation and cardiac contraction, Ca²⁺ levels are regulated by a variety of Ca²⁺-handling proteins. In turn, Ca²⁺ modulates numerous electrophysiological processes. Accordingly, Ca²⁺-handling abnormalities can promote cardiac arrhythmias via various mechanisms, including the promotion of afterdepolarizations, ion-channel modulation and structural remodeling. In the last 30 years, significant improvements have been made in the computational modeling of cardiomyocyte Ca²⁺ handling under physiological and pathological conditions. However, numerous questions involving the Ca²⁺-dependent regulation of different macromolecular complexes, cross-talk between Ca²⁺-dependent regulatory pathways operating over a wide range of time scales, and bidirectional interactions between electrophysiology and mechanics remain to be addressed by in vitro and in silico studies. A better understanding of disease-specific Ca²⁺-dependent proarrhythmic mechanisms may facilitate the development of improved therapeutic strategies. In this review, we describe the fundamental mechanisms of cardiomyocyte Ca²⁺ handling in health and disease, and provide an overview of currently available computational models for cardiomyocyte Ca²⁺ handling. Finally, we discuss important uncertainties and open questions about cardiomyocyte Ca²⁺ handling and highlight how synergy between in vitro and in silico studies may help to answer several of these issues.

钙（Ca ²⁺）在心肌细胞兴奋-收缩偶联中起着核心作用。为了确保最佳的电脉冲传播和心脏收缩，Ca ^2+的水平由多种Ca ^2+处理蛋白调节。进而，Ca ²⁺调节许多电生理过程。因此，Ca ^2+处理异常可通过多种机制促进心律失常，包括促进去极化，离子通道调节和结构重塑。在过去的30年中，心肌细胞Ca ²⁺的计算模型已经取得了重大进步。在生理和病理条件下的处理。但是，涉及钙许多问题²⁺不同的大分子复合物，钙之间的串扰的依赖监管²⁺依赖的调节通路在大范围的时间尺度上的操作，以及电和机械之间的双向互动仍待解决的体外和计算机模拟研究。对特定于疾病的Ca ²⁺依赖的心律失常机制的更好理解可能有助于改进治疗策略的发展。在这篇综述中，我们描述了心肌细胞Ca ²⁺的基本机制处理健康和疾病，并概述了心肌Ca ²⁺处理的当前可用计算模型。最后，我们讨论了有关心肌细胞Ca ²⁺处理的重要不确定性和悬而未决的问题，并强调了体外和计算机模拟研究之间的协同作用如何帮助回答其中一些问题。