慢性房颤患者心房肌细胞乙酰胆碱敏感钾通道的研究

Acetylcholine sensitive K^+ channel (K_(ACh)) in chronic human atrial fibrillation

目的:研究慢性房颤时乙酰胆碱敏感钾通道电流及其基因表达的变化,探讨该离子通道变化在房颤发生与发展中的作用。方法:膜片钳全细胞技术记录风湿性心脏病慢性房颤患者和窦性心律患者心房肌细胞乙酰胆碱敏感钾通道电流,分析两组的电流密度-电压关系曲线;半定量逆转录聚合酶链式反应(RT-PCR)测量心房肌细胞乙酰胆碱敏感钾通道基因(Kir3·4)mRNA表达的变化。结果:(1)与窦性心律组比较,在测试电位-80mV--120mV时,慢性房颤组心房肌细胞乙酰胆碱敏感钾通道电流密度明显减小。其中测试电位为-100mV时,慢性房颤组电流密度为(-11·665±1·027)pA/pF(n=11),窦性心律组为(-19·486±0·766)pA/pF(n=11)(P<0·01)。(2)慢性房颤组心房肌细胞Kir3·4mRNA表达低于窦性心律组54·3%,为0·523±0·301(n=11)vs0·239±0·102(n=11),P<0·01。结论:慢性房颤时乙酰胆碱敏感钾通道电流密度的改变与乙酰胆碱敏感钾通道基因表达下调呈正相关,该通道的改变可能与房颤的发生和发展有关。

AIM： To investigate the changes of current and gene expression of acetylcholine sensitive K^＋ channel （KACh） in chronic human atrial fibrillation （AF） and to evaluate the roles of KACh expression in the occurring and maintence of AF. METHODS： Acetylcholine sensitive K^＋ currents （IKACh） were recorded with the whole-cell patch clamp technique in single atrial myocyte of AF group and normal sinus rhythm group （ SR group）. The current densities - voltage relations were analyzed. The Kir3.4 mRNA was measured by reverse transcription- polymerase chain reaction. RESULTS： （1） Compared with SR group, acetylcholine sensitive K^＋ current densities in AF group were reduced under testing potential between - 80 mV and - 120 inV. Acetylcholine sensitive K^＋ current density was （ - 11.665 ± 1.027） pA/pF （ n = 11 ） in AF group vs （ - 19.486 ± 0.766） pA/pF （n=11） in SR group at -100 mV testing potential （P〈0.01）. （2）Compared with SR group, Kir3.4 mRNA in AF group decreased by 54.30/0 （0.523±0.301 vs 0.239±0.102, n= 11, P〈0.01）. CONCLUSIONS： There is positive relation between down - regulation in channel mRNA.level and alterations in ion current density. These changes of KACh possibly contribute to the occurring and maintenance of AF.