Key Lab of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China; Department of Pharmacology, University of California, Davis, CA 95616, USA.
J Zhejiang Univ Sci B. 2014 Mar;15(3):201-11. doi: 10.1631/jzus.B1300177.
T-wave alternans, a specific form of cardiac alternans, has been associated with the increased susceptibility to cardiac arrhythmias and sudden cardiac death (SCD). Plenty of evidence has related cardiac alternans at the tissue level to the instability of voltage kinetics or Ca(2+) handling dynamics at the cellular level. However, to date, none of the existing experiments could identify the exact cellular mechanism of cardiac alternans due to the bi-directional coupling between voltage kinetics and Ca(2+) handling dynamics. Either of these systems could be the origin of alternans and the other follows as a secondary change, therefore making the cellular mechanism of alternans a difficult chicken or egg problem. In this context, theoretical analysis combined with experimental techniques provides a possibility to explore this problem. In this review, we will summarize the experimental and theoretical advances in understanding the cellular mechanism of alternans. We focus on the roles of action potential duration (APD) restitution and Ca(2+) handling dynamics in the genesis of alternans and show how the theoretical analysis combined with experimental techniques has provided us a new insight into the cellular mechanism of alternans. We also discuss the possible reasons of increased propensity for alternans in heart failure (HF) and the new possible therapeutic targets. Finally, according to the level of electrophysiological recording techniques and theoretical strategies, we list some critical experimental or theoretical challenges which may help to determine the origin of alternans and to find more effective therapeutic targets in the future.
T 波电交替是一种特定形式的心脏电交替，与心律失常和心脏性猝死（SCD）的易感性增加有关。大量证据表明，组织水平的心脏电交替与细胞水平的电压动力学或 Ca(2+)处理动力学的不稳定性有关。然而，迄今为止，由于电压动力学和 Ca(2+)处理动力学之间的双向耦合，由于存在双向耦合，没有一项现有实验能够确定心脏电交替的确切细胞机制。这两个系统中的任何一个都可能是电交替的起源，而另一个则是继发变化，因此使电交替的细胞机制成为一个难以解决的鸡或蛋问题。在这种情况下，理论分析与实验技术相结合提供了探索这个问题的可能性。在这篇综述中，我们将总结理解电交替细胞机制的实验和理论进展。我们重点介绍动作电位时程（APD）复极和 Ca(2+)处理动力学在电交替产生中的作用，并展示理论分析与实验技术相结合如何为我们提供对电交替细胞机制的新见解。我们还讨论了心力衰竭（HF）中电交替易感性增加的可能原因和新的可能治疗靶点。最后，根据电生理记录技术和理论策略的水平，我们列出了一些可能有助于确定电交替起源并在未来找到更有效的治疗靶点的关键实验或理论挑战。
