title: Cardiac-specific overexpression of SCN5A gene leads to shorter P wave duration and PR interval in transgenic mice.
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).
authors.affiliation: Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute/NE40, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.forename: Sandro L
authors.initials: SL
authors.lastname: Yong
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Tian
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics; D004562:Electrocardiography; D015870:Gene Expression; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; C568321:Scn5a protein, mouse; D015222:Sodium Channels