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

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。

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

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 cultured atrium-derived myocytes (HL-1 cells), knockdown of Cx43 significantly inhibited the mRNA expression of L-type calcium channel α1c subunit, as well as L-type calcium current. Co-localization of Cx43 with L-type calcium channel α1c 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.