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首页> 外文期刊>Cell communication & adhesion >Pharmacological Enhancement of Cardiac Gap Junction Coupling Prevents Arrhythmias in Canine LQT2 Model
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Pharmacological Enhancement of Cardiac Gap Junction Coupling Prevents Arrhythmias in Canine LQT2 Model

机译:心脏间隙连接偶联的药理作用增强可预防犬LQT2模型中的心律失常

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摘要

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.
机译:在正常心脏中以及在患病心脏中QT间隔延长的情况下,间隙连接有助于复极的透壁异质性。这项研究检查了在犬LQT2模型中增强间隙连接耦合是否可以减少跨壁的复极色散(TDR)并防止扭转尖端(TdP)。用延迟整流钾电流(IKr)阻断剂d-索他洛尔灌注犬左心室楔形制剂以模拟LQT2,并将抗心律不齐肽10(AAP10)用作间隙连接偶联增强剂。与对照组相比,LQT2组的TDR显着增加,TdP的发生率与非磷酸化连接蛋白43(Cx43)增加有关。 AAP10在挽救Cx43磷酸化的同时防止了TDR的增加和TdP的诱导。 Cx43的数量和空间分布没有明显变化。这些数据表明,间隙连接增强子AAP10可以通过防止LQT2模型中Cx43的去磷酸化来防止TDR的增加并抑制TdP。

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