Abstract 14883: Atrial SERCA2a Overexpression Has No Effect on Cardiac Alternans but Promotes Arrhythmogenic SR Calcium Triggers
Background: Atrial fibrillation (AF) is the most common arrhythmia in humans yet; treatment for AF has remained sub-optimal due to a poor understanding of the underlying mechanisms. Cardiac alternans has been found to precede AF episodes, suggesting an important arrhythmia substrate. Recently, we demonstrated that SERCA2a overexpression suppresses cardiac alternans and arrhythmias in the ventricle. Therefore, we hypothesized that SERCA2a overexpression will decrease cardiac alternans and arrhythmias in the atrium.
Methods: Adult rat isolated atrial myocytes where divided into three treatment groups 1) Control, 2) SERCA2a overexpression (Ad.SERCA2a) and 3) SERCA2a inhibition (Thapsigargin, 1μm). Intracellular Ca2+ was measured using Indo-1AM and Ca2+ alternans (Ca-ALT) was induced with a standard ramp pacing protocol.
Results: As predicted, SR Ca2+ reuptake was enhanced with SERCA2a overexpression (p < 0.05) and reduced with SERCA2a inhibition (p < 0.05) when compared to control myocytes. Surprisingly, there was no difference in susceptibility to Ca-ALT with either SERCA2a overexpression or inhibition when compared to controls (p = 0.73). In contrast, SERCA2a overexpression resulted in increased spontaneous SR Ca2+ release events compared to inhibition and control myocytes (28%, 0% and 0%, respectively, p < 0.05), and a concomitant increase in SR Ca2+ load compared to control (p < 0.05). Based on these observations we tested in vivo atrial arrhythmia inducibility in control and Ad.SERCA2a animals using an esophageal burst atrial pacing protocol. There were no inducible atrial arrhythmias in Ad.GFP (n=4) animals though 25% of Ad.SERCA2a (n=4) animals had inducible atrial arrhythmias (p = 0.28).
Conclusions: Our findings suggest that unlike the ventricle, SERCA2a is not a key regulator of cardiac alternans in the atrium. Importantly, SERCA2a overexpression in atrial myocytes can increase spontaneous SR Ca2+ release, which may be arrhythmogenic.
Author Disclosures: M.M. Jennings: None. X. Wan: None. K.R. Laurita: None. M.J. Cutler: Honoraria; Modest; Boston Scientific.
- © 2014 by American Heart Association, Inc.