Differential effects of the peroxynitrite donor, SIN-1, on atrial and ventricular myocyte electrophysiology.


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 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), 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, whereas 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 in 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.

DOI: 10.1097/FJC.0b013e31828748ca

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@article{Bonilla2013DifferentialEO, title={Differential effects of the peroxynitrite donor, SIN-1, on atrial and ventricular myocyte electrophysiology.}, author={Ingrid M. Bonilla and Arun Raghav Mahankali Sridhar and Yoshinori Nishijima and S{\'a}ndor Gy{\"{o}rke and Arturo J. Cardounel and Cynthia A. Carnes}, journal={Journal of cardiovascular pharmacology}, year={2013}, volume={61 5}, pages={401-7} }