Referenced in: none

Automatically associated channels: Kv7.1 , Nav1.5

Title: Atrial arrhythmogenic properties in wild-type and Scn5a+/- murine hearts.

Authors: Yana Dautova, Yanmin Zhang, Andrew A Grace, Christopher L-H Huang

Journal, date & volume: Exp. Physiol., 2010 Oct , 95, 994-1007

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20621962

Abstract
Loss- and gain-of-function cardiac Na(+) channel (SCN5A) mutations are associated with the Brugada and long QT type 3 syndromes (LQT3), respectively. Both result in ventricular arrhythmias, but have differing atrial effects. We have recently reported decreased incidences of atrial arrhythmias in a murine Scn5a+/Delta cardiac system used to model LQT3. We now explore for atrial arrhythmias in a murine Brugada syndrome model. Programmed electrical stimulation and burst pacing were applied to 10 wild-type (WT) and 10 Scn5a+/- Langendorff-perfused murine hearts. These induced arrhythmias in similar proportions of the Scn5a+/- and WT hearts, in contrast to their decreased incidences previously reported for Scn5a+/Delta. Almost half of the Scn5a+/- hearts displayed spontaneous atrial arrhythmias never observed in WT. Both these WT and Scn5a+/- hearts showed positive critical intervals, given by the difference between action potential durations at 90% recovery (APD(90)) and atrial effective refractory periods, before pharmacological intervention. Both flecainide and quinidine then prevented both induced and spontaneous atrial arrhythmias in all the arrhythmic WT and Scn5a+/- hearts, in contrast to their differing ventricular effects. However, flecainide prolonged APD(90) in WT but not Scn5a+/-, whereas quinidine prolonged APD(90) in both WT and Scn5a+/-. Nevertheless, addition of both agents markedly increased atrial effective refractory periods to values exceeding the corresponding values of APD(90). This resulted in negative critical intervals in both WT and Scn5a+/-. These findings demonstrate a clear-cut relationship between critical interval and atrial arrhythmic tendency for the first time and extend previous reports that had related critical interval to ventricular arrhythmia.