Abstract 16882: Over Expression of Scn5a in Mouse Heart Mimics Human Syndrome of Enhanced Atrioventricular Nodal Conduction
Introduction: The mechanism of enhanced atrioventricular nodal conduction (EAVNC), including Lown-Ganong-Levine (LGL) syndrome, is not well described. Transgenic mice with the over-expression SCN5A results in a shorter P-R interval; hence, we tested the hypothesis that overexpression of SCN5A may provide an animal model mimicking EAVNC.
Methods: Electrocardiogram (ECG), atrial, His-bundle and ventricular electrograms were recorded from wild type (WT) and transgenic mice over-expressing SCN5A (TG). Peak Na+ current (INa) and Nav1.5 expression were measured using patch-clamp technique and immunohistochemistry method, respectively.
Results: P-R interval in TG was much shorter than in WT mice (13.6±1.20 vs. 40.2±0.59 ms, n=20 and 35). In TG isolated hearts the A-V conduction during right atrial pacing remains shorter than that of WT isolated hearts (14.4±0.81 vs. 39.5±0.62 ms, n=28 each). His-bundle electrogram (HBE) revealed a short A-H and H-V intervals in TG, compared to WT mice (Figure 1A-D). In addition, TG mice had a short Wenckebach cycle length (CL) and atrioventricular effective refractory period (AVERP). Peak INa was 2-fold greater in TG compared to WT ventricular myocytes (198.2±16.22 vs. 89.6±5.35 pA/pF, n=12). Flecainide (6 μM, n=6) led to prolongation of A-V conduction time in TG to a value close to that of WT hearts. Nifedipine (1 μM, n=) prolonged A-H interval in WT but not in TG hearts. Immunohistochemistry studies revealed increased Nav1.5 labeling in TG atrial and ventricular tissue, and Nav1.5 expression in A-V junction and A-V ring regions of TG compared to WT hearts.
Conclusion: SCN5A over expression in TG mice enhanced the A-V conduction mimicking EAVNC. Thus, higher level of sodium channel expression in the A-V nodal region may be an electrophysiological substrate responsible for the syndrome of EAVNC. Figure 1
Author Disclosures: G. Liu: None. L. Belardinelli: None. S. Rajamani: None. C. Remme: None. B. Boukens: None.
- © 2014 by American Heart Association, Inc.