Qu Zhilin, Hanna Peter, Ajijola Olujimi A, Garfinkel Alan, Shivkumar Kalyanam
UCLA Cardiac Arrhythmia Center and Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
J Physiol. 2025 Mar;603(7):1887-1901. doi: 10.1113/JP287632. Epub 2024 Nov 29.
The standard conception of cardiac conduction is based on the cable theory of nerve conduction, which treats cardiac tissue as a continuous syncytium described by the Hodgkin-Huxley equations. However, cardiac tissue is composed of discretized cells with microscopic and macroscopic heterogeneities and discontinuities, such as subcellular localizations of sodium channels and connexins. In addition to this, there are heterogeneities in the distribution of sympathetic and parasympathetic nerves, which powerfully regulate impulse propagation. In the continuous models, the ultrastructural details, i.e. the microscopic heterogeneities and discontinuities, are ignored by 'coarse graining' or 'smoothing'. However, these ultrastructural components may play crucial roles in cardiac conduction and arrhythmogenesis, particularly in disease states. We discuss the current progress of modelling the effects of ultrastructural components on electrical conduction, the issues and challenges faced by the cardiac modelling community, and how to scale up conduction properties at the subcellular (microscopic) scale to the tissue and whole-heart (macroscopic) scale in future modelling and experimental studies, i.e. how to link the ultrastructure at different scales to impulse conduction and arrhythmogenesis in the heart.
心脏传导的标准概念基于神经传导的电缆理论，该理论将心脏组织视为由霍奇金 - 赫胥黎方程描述的连续合胞体。然而，心脏组织是由具有微观和宏观异质性及不连续性的离散细胞组成，例如钠通道和连接蛋白的亚细胞定位。除此之外，交感神经和副交感神经的分布也存在异质性，它们对冲动传播有强大的调节作用。在连续模型中，超微结构细节，即微观异质性和不连续性，通过“粗粒化”或“平滑”被忽略。然而，这些超微结构成分可能在心脏传导和心律失常发生中起关键作用，特别是在疾病状态下。我们讨论了模拟超微结构成分对电传导影响的当前进展、心脏建模领域面临的问题和挑战，以及在未来建模和实验研究中如何将亚细胞（微观）尺度的传导特性扩展到组织和全心（宏观）尺度，即如何将不同尺度的超微结构与心脏中的冲动传导和心律失常发生联系起来。
