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

作　　者：Yun-liang ZANG Ling XIA 

机构地区：[1]Key Lab of Biomedical Engineering of Ministrv of Edueation, Department of Biomedieal Engineering, ZheJiang Universitv, Hangzhou 310027, China) [2]Department of Pharmacology, University of California, Davis, CA 95616, USA

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2014年第3期201-211,共11页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：Project supported by the National Basic Research Program （973） of China （No. 2007CB512100） and the National Natural Science Foun- dation of China （Nos. 81171421 and 61101046）

摘　　要：T-wave alternans, a specific form of cardiac alternans, has been associated with the increased suscep- tibility 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 tar- gets in the future.

关 键 词：Cardiac alternans Action potential duration （APD） restitution Ca^2＋ handling Heart failure 

分 类 号：R541.7[医药卫生—心血管疾病]