Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 645721, 8 pages
Research Article

Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes

1Department of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43221, USA
2College of Pharmacy, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
3Translational Medicine Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA

Received 20 April 2012; Revised 13 July 2012; Accepted 16 July 2012

Academic Editor: Christopher Ahern

Copyright © 2012 Honglan Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3−/−) exhibit prolonged action potential (AP) duration and enhanced spontaneous activity (early and delayed afterdepolarizations) during β-adrenergic (β-AR) stimulation. Studies have shown that nitric oxide is able to regulate various K+ channels. Our objective was to examine if NOS3-/- myocytes had altered K+ currents. APs, transient outward ( 𝐼 t o ), sustained ( 𝐼 K s u s ), and inward rectifier ( 𝐼 K 1 ) K+ currents were measured in NOS3-/- and wild-type (WT) myocytes. During β-AR stimulation, AP duration (measured as 90% repolarization-APD90) was prolonged in NOS3−/− compared to WT myocytes. Nevertheless, we did not observe differences in 𝐼 t o , 𝐼 K s u s , or 𝐼 K 1 between WT and NOS3−/− myocytes. Our previous work showed that NOS3−/− myocytes had a greater Ca2+ influx via L-type Ca2+ channels with β-AR stimulation. Thus, we measured β-AR-stimulated SR Ca2+ load and found a greater increase in NOS3−/− versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3−/− myocytes is not due to changes in 𝐼 t o , 𝐼 K s u s , or 𝐼 K 1 . Furthermore, the increase in spontaneous activity in NOS3−/− myocytes may be due to a greater increase in SR Ca2+ load. This may have important implications for heart failure patients, where arrhythmias are increased and NOS3 expression is decreased.