JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Cellular mechanism of cardiac alternans: an unresolved chicken or egg problem

Author(s): Yun-liang Zang^1;2, Ling Xia¹
Affiliation(s): 1. Key Lab of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China;2. Department of Pharmacology, University of California, Davis, CA 95616, USA
Corresponding email(s): xialing@zju.edu.cn
Key Words: Cardiac alternans, Action potential duration (APD) restitution, Ca handling, Heart failure

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Yun-liang Zang, Ling Xia. Cellular mechanism of cardiac alternans: an unresolved chicken or egg problem[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B1300177

@article{title="Cellular mechanism of cardiac alternans: an unresolved chicken or egg problem",
author="Yun-liang Zang, Ling Xia",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B1300177"
}

%0 Journal Article
%T Cellular mechanism of cardiac alternans: an unresolved chicken or egg problem
%A Yun-liang Zang
%A Ling Xia
%J Journal of Zhejiang University SCIENCE B
%P 201-211
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B1300177"

TY - JOUR
T1 - Cellular mechanism of cardiac alternans: an unresolved chicken or egg problem
A1 - Yun-liang Zang
A1 - Ling Xia
J0 - Journal of Zhejiang University Science B
SP - 201
EP - 211
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B1300177"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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.

心脏电交替现象的细胞机制：先有鸡还是先有蛋的谜团

研究目的：探索心脏电交替（alternans）现象的细胞支持机制，从而能够更有针对性地抑制alternans，进而优化治疗心律失常。
创新要点：采用理论方法系统探索离子流以及钙循环系统异常对alternans形成的影响。由于两个系统的互相影响，实验上无法有效地对二者的作用分别进行定量研究。
研究方法：结合实验数据，建立理论模型，并结合非线性动力学知识，定量分析离子流和钙循环各成分对alternans形成的相对贡献。
重要结论：理论分析结合实验数据对于认识alternans发生机制有着重要意义，对未来更有针对性治疗心律失常提供了一种新的路径。

关键词组：交替（Alternans）；心律失常；离子流；钙循环；模型

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心脏电交替现象的细胞机制：先有鸡还是先有蛋的谜团

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References