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Transcriptional profiles of genes related to electrophysiological function in Scn5a +/− murine hearts

Takla, Michael, Edling, Charlotte E., Zhang, Kevin, Saadeh, Khalil, Tse, Gary, Salvage, Samantha C., Huang, Christopher L.‐H., Jeevaratnam, Kamalan (2021) Transcriptional profiles of genes related to electrophysiological function in Scn5a +/− murine hearts. Physiological Reports, 9 (19). Article Number e15043. ISSN 2051-817X. (doi:10.14814/phy2.15043) (KAR id:98732)


The Scn5a gene encodes the major pore-forming Nav1.5 (α) subunit, of the voltage-gated Na+ channel in cardiomyocytes. The key role of Nav1.5 in action potential initiation and propagation in both atria and ventricles predisposes organisms lacking Scn5a or carrying Scn5a mutations to cardiac arrhythmogenesis. Loss-of-function Nav1.5 genetic abnormalities account for many cases of the human arrhythmic disorder Brugada syndrome (BrS) and related conduction disorders. A murine model with a heterozygous Scn5a deletion recapitulates many electrophysiological phenotypes of BrS. This study examines the relationships between its Scn5a+/− genotype, resulting transcriptional changes, and the consequent phenotypic presentations of BrS. Of 62 selected protein-coding genes related to cardiomyocyte electrophysiological or homeostatic function, concentrations of mRNA transcribed from 15 differed significantly from wild type (WT). Despite halving apparent ventricular Scn5a transcription heterozygous deletion did not significantly downregulate its atrial expression, raising possibilities of atria-specific feedback mechanisms. Most of the remaining 14 genes whose expression differed significantly between WT and Scn5a+/− animals involved Ca2+ homeostasis specifically in atrial tissue, with no overlap with any ventricular changes. All statistically significant changes in expression were upregulations in the atria and downregulations in the ventricles. This investigation demonstrates the value of future experiments exploring for and clarifying links between transcriptional control of Scn5a and of genes whose protein products coordinate Ca2+ regulation and examining their possible roles in BrS.

Item Type: Article
DOI/Identification number: 10.14814/phy2.15043
Subjects: R Medicine
Divisions: Divisions > Division of Natural Sciences > Kent and Medway Medical School
Depositing User: Manfred Gschwandtner
Date Deposited: 06 Dec 2022 11:27 UTC
Last Modified: 08 Dec 2022 09:56 UTC
Resource URI: (The current URI for this page, for reference purposes)

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