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Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?

BACKGROUND: Alterations in the SCN5A gene encoding the cardiac sodium channel Na(v)1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden d...

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Detalles Bibliográficos
Autores principales: Scheiper-Welling, Stefanie, Zuccolini, Paolo, Rauh, Oliver, Beckmann, Britt-Maria, Geisen, Christof, Moroni, Anna, Thiel, Gerhard, Kauferstein, Silke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678220/
https://www.ncbi.nlm.nih.gov/pubmed/33213388
http://dx.doi.org/10.1186/s12881-020-01170-3
Descripción
Sumario:BACKGROUND: Alterations in the SCN5A gene encoding the cardiac sodium channel Na(v)1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.316A > G, p.(Ser106Gly) in a 35-year-old patient with survived cardiac arrest. In the present study, we aimed to investigate the functional impact of the variant to clarify the medical relevance. METHODS: Mutant as well as wild type GFP tagged Na(v)1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique. RESULTS: Electrophysiological measurements indicated, that the detected missense variant alters Nav1.5 channel functionality leading to a gain-of-function effect. Cells expressing S106G channels show an increase in Na(v)1.5 current over the entire voltage window. CONCLUSION: The results support the assumption that the detected sequence aberration alters Na(v)1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12881-020-01170-3.