Abstract 11401: Electrophysiological Basis for Atrial Arrhythmia in a Long QT Syndrome Mouse Model

Introduction: Long-QT syndromes (LQTSs) are known to cause ventricular tachyarrhythmias, but increasing evidence indicates they can also cause atrial fibrillation. Although atrial early afterdepolarizations (EADs) are a plausible cause, there are no published studies of cellular arrhythmia mechanisms at the atrial level in models of congenital LQTS. We therefore studied atrial-cellular electrophysiology in mice with an LQTS-3 SCN5A inactivation-impairing mutation (ΔKPQ) and matched littermate controls (WT). Methods: Late Na+ current (INaL) was measured with whole-cell patch-clamp. Transmembrane action potentials (APs) were recorded with floating microelectrodes from the epicardial side of the isolated left atrium, paced at 6 frequencies between 0.5 and 10 Hz, at 35°C (pH 7.4). Ranolazine (10 μM) was used as an INaL-blocker. Results: As expected, INaL was increased in atrial myocytes of ΔKPQ mice (Figure A). APs in ΔKPQ-mice were significantly prolonged over all frequencies. AP-duration (APD) prolongation ...