Quan Xiao-Qing, Bai Rong, Lu Jia-Gao, Patel Chinmay, Liu Nian, Ruan Yanfei, Chen Bo-Di, Ruan Lei, Zhang Cun-Tai
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell Commun Adhes. 2009;16(1-3):29-38. doi: 10.1080/15419060903118567.
Gap junctions contribute to the transmural heterogeneity of repolarization in the normal heart and under conditions of prolonged QT interval in the diseased heart. This study examined whether enhancing of gap junction coupling can reduce transmural dispersion of repolarization (TDR) and prevent torsade de pointes (TdP) in a canine LQT2 model. Canine left ventricular wedge preparations were perfused with delayed rectifier potassium current (IKr) blocker d-sotalol to mimic LQT2 and the antiarrhythmic peptide 10 (AAP10) was used as a gap junction coupling enhancer. As compared with the control group, the LQT2 group had significantly augmented TDR and higher incidence of TdP associated with increased nonphosphorylated connexin 43 (Cx43). AAP10 prevented augmentation of TDR and induction of TdP while rescuing Cx43 phosphorylation. There was no significant change in the quantity and spatial distribution of Cx43. These data indicate that gap junction enhancer AAP10 can prevent augmentation of TDR and suppress TdP by preventing dephosphorylation of Cx43 in a LQT2 model.
缝隙连接在正常心脏的复极化跨壁异质性以及患病心脏QT间期延长的情况下起作用。本研究检测了增强缝隙连接耦联是否能减少复极化跨壁离散度（TDR）并预防犬LQT2模型中的尖端扭转型室速（TdP）。用延迟整流钾电流（IKr）阻滞剂d - 索他洛尔灌注犬左心室楔形标本以模拟LQT2，并使用抗心律失常肽10（AAP10）作为缝隙连接耦联增强剂。与对照组相比，LQT2组的TDR显著增加，TdP发生率更高，且与非磷酸化连接蛋白43（Cx43）增加有关。AAP10可预防TDR增加和TdP的诱发，同时挽救Cx43的磷酸化。Cx43的数量和空间分布没有显著变化。这些数据表明，缝隙连接增强剂AAP10可通过防止LQT2模型中Cx43的去磷酸化来预防TDR增加并抑制TdP。
