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

Biochem Biophys Res Commun. 2007 Apr 6;355(2):444-50. doi: 10.1016/j.bbrc.2007.01.170. Epub 2007 Feb 7.

Abstract

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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Arrhythmias, Cardiac / genetics
  • Electrocardiography
  • Gene Expression*
  • Heart / physiology
  • Heart / physiopathology
  • Heart Rate
  • Humans
  • Mice
  • Mice, Transgenic
  • NAV1.5 Voltage-Gated Sodium Channel
  • Phenotype
  • Sodium Channels / genetics*

Substances

  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Scn5a protein, mouse
  • Sodium Channels