缝隙连接蛋白43通过调控L型钙电流参与心房肌细胞的电重塑  

Cx43 is involved in electrical remodeling of atrial myocytes through regulating L-type calcium current

作　　者：饶芳[1,2,3] 薛玉梅[1,3] 邓春玉[2,3] 余细勇[1,2,3] 肖定璋[2,3] 陈少贤[2,3] 林秋雄[2,3] 杨慧[2,3] 邝素娟[2,3] 刘晓颖[2,3] 朱杰宁[2,3] 吴书林[1,3] 

机构地区：[1]广东省心血管病研究所心内科 [2]广东省人民医院医学研究部 [3]广东省医学科学院,广东广州510080

出　　处：《中国病理生理杂志》2015年第11期1986-1991,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81370295;No.81470440);广东省自然科学基金资助项目(No.S2013010016256);广东省医学科研基金资助项目(No.A2013049)

摘　　要：目的:观察缝隙连接蛋白43(Cx43)是否通过与L型钙通道共定位,调控L型钙电流,参与房颤(AF)的发病机制。方法:使用蛋白免疫印迹和实时荧光定量PCR检测AF和窦性心律患者心房组织中Cx43的蛋白和mRNA表达差异;用RNA干扰技术沉默心房肌细胞的Cx43表达,实时荧光定量PCR和全细胞膜片钳实验观察对L型钙通道mRNA表达和L型钙电流的影响;免疫共沉淀和激光共聚焦显微成像观察心房肌细胞中Cx43与L型钙通道是否存在共定位。结果:AF患者心房组织中的Cx43表达明显低于窦性心律患者;干扰Cx43表达可明显抑制L型钙电流和L型钙通道α1c亚基的mRNA表达;且心房肌细胞中Cx43与L型钙通道存在共定位。结论:心房肌细胞中的Cx43可通过与L型钙通道形成分子复合物,调控L型钙电流,参与心房肌细胞的电重塑。AIM： To investigate whether the association of connexin 43 （ Cx43 ） and L-type calcium channel involved in the pathogenesis of atrial fibrillation （AF）. METHODS： The biochemical assays and whole-cell patch-clamp technique were used to study the expression of Cx43 in human atrial tissue. The co-localization of Cx43 and L -type calcium channel, and the regulation of L-type calcium current in atrial myocytes were investigated. RESULTS： The expression of Cx43 at mRNA and protein levels was decreased in human atrial tissues of AF patients. In euhured atrium-derived myocytes （HL-1 cells）, knoekdown of Cx43 significantly inhibited the mRNA expression of L-type calcium channel ctl c subunit, as well as L-type calcium current. Co-localization of Cx43 with L-type calcium channel c^lc subunit in mouse atrial myocytes was observed. CONCLUSION： The decrease in Cx43 is involved in the pathogenesis of AF, probably through reducing the L-type calcium current in atrial myoctyes by co-localization with L-type calcium channel, thus representing the potential pathogenesis in atrial fibrillation.

关 键 词：缝隙连接蛋白43 L型钙通道 心房肌细胞 心房纤颤 电重塑 

分 类 号：R363.2[医药卫生—病理学]