Cardiac-specific overexpression of SCN5A gene leads to shorter P wave duration and PR interval in transgenic mice

• Published in: Biochemical and biophysical research communications 2007-04, Vol.355 (2), p.444-450
• Main Authors: Zhang, Teng, Yong, Sandro L., Tian, Xiao-Li, Wang, Qing K.
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Arrhythmias, Cardiac - genetics; Cardiac sodium channel gene SCN5A; Electrocardiogram (ECG); Electrocardiography; Gene Expression; Heart - physiology; Heart - physiopathology; Heart Rate; Humans; Long QT syndrome (LQTS); Mice; Mice, Transgenic; NAV1.5 Voltage-Gated Sodium Channel; P wave and PR interval; Phenotype; Sodium Channels - genetics; Sodium current; Transgenic mice; Ventricular arrhythmias or tachycardia (VT)
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.01.170

The Cardiac sodium channel gene SCN5A plays a critical role in cardiac electrophysiology and its mutations, either gain- or loss-of-functions, are associated with lethal arrhythmias. In this study, we investigated the effect of overexpression of SCN5A on the cardiac phenotype in a transgenic mouse model (TG-WT L10). Compared to NTG mice, heart rate, QRS duration, and QT intervals remained unchanged in TG-WT mice. Moreover, no spontaneous ventricular arrhythmias were detected in TG-WT hearts. Despite these results, a mild, irregular cardiac phenotype was observed in TG-WT mice. The P wave and PR interval were significantly shorter in TG-WT compared with NTG mice (P, 8.8 ± 0.8 ms vs. 12.6 ± 0.9 ms; PR, 12.5 ± 2 ms vs. 33.5 ± 0.7 ms). Furthermore, spontaneous premature atrial contractions were often detected in TG-WT mice. These results suggest that the expression level of the SCN5A gene is a determinant for the length of the P wave duration and PR interval on electrocardiograms (ECG).