Differential effects of the peroxynitrite donor, SIN-1, on atrial and ventricular myocyte electrophysiology.
Differential effects of the peroxynitrite donor, SIN-1, on atrial and ventricular myocyte electrophysiology.
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DOI：
10.1097/fjc.0b013e31828748ca
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发表时间：
2013-05
影响因子：
3
通讯作者：
Carnes CA
中科院分区：
文献类型：
--
作者：
Bonilla IM;Sridhar A;Nishijima Y;Györke S;Cardounel AJ;Carnes CA
氧化应激与心力衰竭和房颤的发病机制有关，可导致心肌中过氧亚硝酸盐的产生增加。用过氧亚硝基阴离子供体SIN-1（3-morpholinosynonimine N-ethylcarbamide）灌流犬心房和心室肌细胞，观察过氧亚硝基阴离子的急性电生理效应。采用穿孔全细胞膜片钳技术记录动作电位。SIN-1（200 μM）可增加心房和心室肌细胞的动作电位时程（APD）;然而，在心房中，APD延长不依赖于心率，而在心室中，APD延长则依赖于心率。除了动作电位的延长外，心室肌细胞的复极搏动变异性显著增加，但心房肌细胞无此现象。我们通过用SERCA阻断剂毒胡萝卜素（5-10 μM）处理心肌细胞来检测细胞内钙循环对SIN-1作用的贡献。抑制钙循环可防止心房和心室肌细胞的APD延长，并防止SIN-1诱导的心室搏动间APD变异性增加。总的来说，这些数据表明，过氧亚硝酸盐影响心房和心室电生理差异。详细了解特定腔室中电生理学的氧化调节对于优化心脏疾病的治疗方法至关重要。
Oxidative stress has been implicated in the pathogenesis of heart failure and atrial fibrillation and can result in increased peroxynitrite production in the myocardium.. Atrial and ventricular canine cardiac myocytes were superfused with SIN-1 (3-morpholinosydnonimine N-ethylcarbamide), a peroxynitrite donor, to evaluate the acute electrophysiologic effects of peroxynitrite. Perforated whole cell patch clamp techniques were used to record action potentials. SIN-1 (200 μM) increased the action potential duration (APD) in atrial and ventricular myocytes; however, in the atria, APD prolongation was rate-independent, while in the ventricle APD prolongation was rate dependent. In addition to prolongation of the action potential, beat to beat variability of repolarization was significantly increased in ventricular, but not atrial myocytes. We examined the contribution of intracellular calcium cycling to the effects of SIN-1 by treating myocytes with the SERCA blocker, thapsigargin (5-10 μM). Inhibition of calcium cycling prevented APD prolongation in the atrial and ventricular myocytes, and prevented the SIN-1 induced increase in ventricular beat to beat APD variability. Collectively, these data demonstrate that peroxynitrite affects atrial and ventricular electrophysiology differentially. A detailed understanding of oxidative modulation of electrophysiology in specific chambers is critical to optimize therapeutic approaches for cardiac diseases.