Guo Donglin, Yu Mengfei, Liu Qinghua, Cox Robert H, Liu Tengxian, Yan Gan-Xin
Lankenau Institute for Medical Research, Wynnewood, PA; College of Life Science, South-Central University for Nationalities, Wuhan, China.
College of Life Science, South-Central University for Nationalities, Wuhan, China.
J Electrocardiol. 2014 Sep-Oct;47(5):642-8. doi: 10.1016/j.jelectrocard.2014.04.004. Epub 2014 Apr 13.
The late sodium current (INa-L) contributes importantly to rate-dependent change in action potential duration (APD) and transmural dispersion of repolarization (TDR). However, little is known about the mechanisms of increased APD rate-dependence and amplified TDR in left ventricular hypertrophy (LVH) and failure. The purpose of this study was to investigate the role of INa-L in rate-adaptation of transmural APD heterogeneity.
APD, its rate-dependence and INa-L current were examined in myocytes isolated from the endocardium and epicardium of the control and LVH rabbits. AP was recorded using the standard microelectrode technique, and INa-L was recorded using the whole-cell patch clamp technique.
Early afterdepolarizations (EADs) were frequently recorded in the isolated myocytes of the LVH rabbits but not in those of controls. LVH prolonged APD more significantly in the endocardial myocytes than in the epicardium (31.7±3.4 vs. 21.6±1.5% n=6, p<0.05), leading to a marked increase in TDR. LVH endocardial myocytes exhibited a greater rate-dependent change in APD compared to the epicardial myocytes. INa-L densities were significantly increased in both LVH endocardium and epicardium. However, LVH increased the INa-L density preferentially in the endocardial myocytes compared to the epicardial myocytes (54.5±4.8% vs. 39.2±3.3%, n=6, p<0.05).
Our results demonstrate that LVH increased the INa-L preferentially in the endocardium over the epicardium, which contributes importantly to the stronger rate-dependent change in repolarization and longer APD in the endocardium. This results in an amplified TDR capable of initiating EAD and ventricular arrhythmias.
晚钠电流（INa-L）对动作电位时程（APD）的频率依赖性变化和复极跨壁离散度（TDR）有重要影响。然而，关于左心室肥厚（LVH）和衰竭时APD频率依赖性增加及TDR放大的机制知之甚少。本研究旨在探讨INa-L在跨壁APD异质性频率适应性中的作用。
在对照和LVH兔的心内膜和心外膜分离的心肌细胞中检测APD、其频率依赖性和INa-L电流。使用标准微电极技术记录动作电位（AP），使用全细胞膜片钳技术记录INa-L。
在LVH兔分离的心肌细胞中经常记录到早期后去极化（EADs），而在对照兔中未记录到。LVH使心内膜心肌细胞的APD延长比心外膜更显著（31.7±3.4对21.6±1.5%，n = 6，p<0.05），导致TDR显著增加。与心外膜心肌细胞相比，LVH心内膜心肌细胞的APD表现出更大的频率依赖性变化。LVH心内膜和心外膜的INa-L密度均显著增加。然而，与心外膜心肌细胞相比，LVH优先增加心内膜心肌细胞的INa-L密度（54.5±4.8%对39.2±3.3%，n = 6，p<0.05）。
我们的结果表明，LVH优先增加心内膜而非心外膜的INa-L，这对心内膜更强的复极频率依赖性变化和更长的APD有重要贡献。这导致TDR放大，能够引发EAD和室性心律失常。
