Huang B, Qin D, El-Sherif N
Department of Medicine, State University of New York Health Science Center, Brooklyn 11203, USA.
J Cardiovasc Electrophysiol. 2000 Nov;11(11):1252-61. doi: 10.1046/j.1540-8167.2000.01252.x.
Down-regulation of key K+ channel subunit gene expression and K+ currents is a universal response to cardiac hypertrophy, whatever the cause, including the postmyocardial infarction (post-MI) remodeled heart.
We investigated the hypothesis that down-regulation of K+ channel genes and currents post-MI occurs early and before significant remodeled hypertrophy of the noninfarcted myocardium could be detected. We investigated (1) the incidence of induced ventricular tachyarrhythmias (VT) in 3-day post-MI rat heart; (2) action potential (AP) characteristics of isolated left ventricular (LV) myocytes from sham-operated and 3-day post-MI heart; (3) time course of changes in outward K+ currents Ito-fast(f) and I(K) in isolated myocytes from 3-day and 4-week post-MI noninfarcted LV and compared the changes with sham-operated animals; and (4) changes in the messenger and protein levels of Kv2.1, Kv4.2, and Kv4.3 in the LV and right ventricle of 3-day post-MI heart. Sustained VT was induced in 6 of 10 3-day post-MI rats and in none of 8 sham rats. The membrane capacitance of myocytes isolated from 3-day post-MI noninfarcted LV was not significantly different from control, whereas membrane capacitance 4-week post-MI was significantly higher, reflecting the development of hypertrophy. AP duration was increased and the density of Ito-f and I(K) were significantly decreased in 3-day post-MI LV myocytes compared with sham. The reduced density of Ito did not significantly differ in 4-week post-MI LV myocytes, whereas the density of I(K) was decreased further at 4 weeks post-MI. The changes in Ito-f and I(K) correlated with decreased messenger and protein levels of Kv4.2/Kv4.3 and Kv2.1, respectively.
These results support the hypothesis that down-regulation of K+ channel gene expression and current in the post-MI LV occurs early and may be dissociated from the slower time course of post-MI remodeled hypertrophy. These changes may contribute to early arrhythmogenesis of the post-MI heart.
关键钾通道亚基基因表达和钾电流的下调是心脏肥大的普遍反应，无论其病因如何，包括心肌梗死后（post-MI）重构心脏。
我们研究了以下假说，即心肌梗死后钾通道基因和电流的下调发生在早期，且在未梗死心肌出现明显重构肥大之前即可检测到。我们研究了：（1）心肌梗死后3天大鼠心脏中诱发性室性心律失常（VT）的发生率；（2）假手术组和心肌梗死后3天心脏分离的左心室（LV）心肌细胞的动作电位（AP）特征；（3）心肌梗死后3天和4周未梗死左心室分离的心肌细胞外向钾电流Ito-fast(f)和I(K)的变化时间进程，并将这些变化与假手术动物进行比较；（4）心肌梗死后3天心脏左心室和右心室中Kv2.1、Kv4.2和Kv4.3的信使核糖核酸和蛋白质水平的变化。10只心肌梗死后3天的大鼠中有6只诱发出持续性VT，而8只假手术大鼠均未诱发。心肌梗死后3天未梗死左心室分离的心肌细胞膜电容与对照组无显著差异，而心肌梗死后4周膜电容显著更高，反映出肥大的发展。与假手术组相比，心肌梗死后3天左心室心肌细胞的动作电位时程延长，Ito-f和I(K)密度显著降低。心肌梗死后4周左心室心肌细胞Ito密度降低不显著，而心肌梗死后4周I(K)密度进一步降低。Ito-f和I(K)的变化分别与Kv4.2/Kv4.3和Kv2.1信使核糖核酸和蛋白质水平降低相关。
这些结果支持以下假说，即心肌梗死后左心室钾通道基因表达和电流的下调发生在早期，且可能与心肌梗死后重构肥大较慢的时间进程无关。这些变化可能促成心肌梗死后心脏的早期心律失常发生。
