Huang B, Qin D, El-Sherif N
Cardiology Division, Department of Medicine, Box 1199, State University of New York Health Science Center and Veterans Affairs Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Cardiovasc Res. 2001 Nov;52(2):246-54. doi: 10.1016/s0008-6363(01)00378-9.
The hypothesis being tested in the present study is that increased anisotropic properties occurs in the remodeled post-infarction heart due to spatial alterations in Kv channels expression and K(+) currents of the remodeled myocardium.
Three to 4 weeks post myocardial infarction (MI) in the rat, we measured the two components of the outward K(+) current, I(to-fast (f)) and I(to-slow(s)) in the epicardium (epi) and endocardium (endo) of noninfarcted remodeled left ventricle (LV) using patch clamp techniques. Alterations in mRNA and/or protein levels of potassium channel genes Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 were measured in epi, midmyocardium (mid), and endo regions of LV and in the right ventricle (RV).
In sham operated rat heart, the density of I(to-f) was 2.3 times greater in epi compared to endo myocytes. In post-MI heart, the density of I(to-f) and I(to-s) decreased to a similar degree in LV epi and endo but the difference in I(to-f) density between epi and endo persisted. The mRNA and/or protein levels of Kv1.4, Kv2.1, Kv4.2 and Kv4.3 but not Kv1.5 decreased to a varying extent in different regions of LV but not in RV of post-MI heart.
Our results suggest that regional downregulation of Kv channels expression and density of K(+) currents can be a significant determinant of increased spatial electrophysiological heterogeneity and contribute to increased electrical instability of the post-MI heart.
本研究中正在检验的假设是，由于梗死心肌中钾通道表达和钾离子电流的空间改变，梗死后期重塑心脏的各向异性特性增加。
在大鼠心肌梗死（MI）后3至4周，我们使用膜片钳技术测量了未梗死的左心室（LV）的心外膜（epi）和心内膜（endo）中向外钾离子电流的两个成分，即快速延迟整流钾电流（I(to-fast (f))）和缓慢延迟整流钾电流（I(to-slow(s))）。在LV的心外膜、心肌中层（mid）、心内膜区域以及右心室（RV）中测量钾通道基因Kv1.4、Kv1.5、Kv2.1、Kv4.2和Kv4.3的mRNA和/或蛋白质水平的变化。
在假手术大鼠心脏中，心外膜I(to-f)密度比心内膜心肌细胞高2.3倍。在心肌梗死后的心脏中，LV的心外膜和心内膜中I(to-f)和I(to-s)密度以相似程度降低，但心外膜和心内膜之间I(to-f)密度的差异仍然存在。在心肌梗死后心脏的LV不同区域中，Kv1.4、Kv2.1、Kv4.2和Kv4.3的mRNA和/或蛋白质水平不同程度下降，但在RV中未下降。
我们的结果表明，钾通道表达的区域下调和钾离子电流密度可能是空间电生理异质性增加的重要决定因素，并导致心肌梗死后心脏电不稳定性增加。
