Short-term pacing in the mouse alters cardiac expression of connexin43.
Short-term pacing in the mouse alters cardiac expression of connexin43.
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DOI：
10.1186/1472-6793-8-8
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发表时间：
2008-05-06
期刊：
影响因子：
--
通讯作者：
Gutstein DE
中科院分区：
文献类型：
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作者：
Kontogeorgis A;Kaba RA;Kang E;Feig JE;Gupta PP;Ponzio M;Liu F;Rindler MJ;Wit AL;Fisher EA;Peters NS;Gutstein DE
心肌损伤，如缺血、梗死、肥大和扩张，通常伴随着连接蛋白43间隙连接蛋白的丰富和/或定位的改变，这可能易于发生心律失常并发症。慢性不同步心脏激活的模型也被证明导致连接蛋白43在心肌细胞中的重新分布。我们推测，小鼠心脏中连接蛋白43的表达和定位的改变可能是由短时间的心室起搏引起的。在取出心脏进行分析之前，使用隔膜下方法对一系列野生型小鼠进行6小时的起搏。小鼠以高于其平均麻醉窦率10-15%的速度起搏，并进行监测，以确保1：1捕获。短期起搏导致连接蛋白43的mRNA丰度显著降低，连接蛋白43从肌膜部分重新分布到非肌膜部分，泛素化的连接蛋白43积聚，而总体连接蛋白43的蛋白水平没有明显变化。这些早期起搏诱导的缝隙连接蛋白43表达的变化并没有伴随着心功能下降、长期的不稳定或增加对持续性心律失常的诱导性。我们的数据表明，短期起搏与连接蛋白43缝隙连接表达的早期变化有关，可能包括产量减少和降解速度减慢。这种小鼠模型可能有助于研究起搏引起的早期分子变化，并最终可能有助于开发预防缝隙连接重塑和相关的心脏疾病心律失常并发症的策略。
Cardiac insults such as ischemia, infarction, hypertrophy and dilatation are often accompanied by altered abundance and/or localization of the connexin43 gap junction protein, which may predispose towards arrhythmic complications. Models of chronic dyssynchronous cardiac activation have also been shown to result in redistribution of connexin43 in cardiomyocytes. We hypothesized that alterations in connexin43 expression and localization in the mouse heart might be induced by ventricular pacing over a short period of time. The subdiaphragmatic approach was used to pace a series of wild type mice for six hours before the hearts were removed for analysis. Mice were paced at 10–15% above their average anesthetized sinus rate and monitored to ensure 1:1 capture. Short-term pacing resulted in a significant reduction in connexin43 mRNA abundance, a partial redistribution of connexin43 from the sarcolemma to a non-sarcolemmal fraction, and accumulation of ubiquitinated connexin43 without a significant change in overall connexin43 protein levels. These early pacing-induced changes in connexin43 expression were not accompanied by decreased cardiac function, prolonged refractoriness or increased inducibility into sustained arrhythmias. Our data suggest that short-term pacing is associated with incipient changes in the expression of the connexin43 gap junction, possibly including decreased production and a slowed rate of degradation. This murine model may facilitate the study of early molecular changes induced by pacing and may ultimately assist in the development of strategies to prevent gap junction remodeling and the associated arrhythmic complications of cardiac disease.