心力衰竭家兔左室短暂外向钾电流下调的分子基础

Molecular basis of transient outward potassium current downregulation in rabbits with heart failure

目的为探讨心力衰竭(简称心衰)兔左室短暂外向钾电流(Ito)下调的分子基础。方法采用结扎家兔冠状动脉左前降支的方法制备缺血性心衰模型。应用膜片钳全细胞记录方法记录左室心肌细胞Ito,描记电流-电压(I-V)曲线;应用半定量-聚合酶链式反应(RT-PCR)法检测电压依赖性Kv1.4和Kv4.3钾通道α亚单位mRNA表达,并以图象分析系统对其进行半定量分析。结果心衰组家兔左室心肌细胞Ito密度较对照组显著降低,I-V曲线明显下移;指令电压为+70mV时,心衰组Ito密度(9.73±0.94pA/pF,n=5)显著低于对照组(14.35±1.16pA/pF,n=4)(P<0.01)。Kv1.4和Kv4.3钾通道α亚单位mRNA表达心衰组(分别为0.66±0.05,0.21±0.02,n=5)也较对照组(分别为0.95±0.07,0.531±0.04,n=5)显著降低(P均<0.01)。结论心衰家兔左室Ito电流密度下调可能受转录水平调节。

Objective To investigate the molecular basis of transient outward potassium current （Ⅰto） downregulation in rabbits with heart failure（HF）. Methods Rabbits models of HF were established by ligation of the left anterior descending coronary artery. Whole-cell electrophysiological recording was used to study changes of the Ⅰto current density in isolated left ventricular myocytes in rabbits, the curve of Ⅰ-Ⅴ relationship of i,o was depicted. Semi-quantitative RT-PCR was used to examine the mRNA level of Kv1. 4 and Kv4.3 potassium channel α subunit in ventricular tissues. Results Ito current density of myocytes were significantly decreased in rabbits with HF than those of control group. The curve of Ⅰ-Ⅴ of Ⅰto in HF group was decreased. I,o current density （at ＋70 mV） in HF group （9.73 ±0.94 pA/pF） was markedly lower than that of control group（ 14.35 ± 1.16 pA/pF）. The mRNA level of Kv1. 4 and Kv4.3 potassium channel α subunit significantly decreased in failing heart （0.66 ± 0.05,0.21 ± 0.02 ） compared with nonfailing hearts （ 0.95 ± 0.07,0.53 ± 0.04 ）. Conclusions The downregulation of Ⅰto current density in heart failure may be transcriptionally regulated.