Selectivity Filter Mutation in NaV1.5 Promotes Ventricular Tachycardia

JACC. Clinical electrophysiology 2026 Open access

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Authors: Zoja Selimi, Mikhail Tarasov, Xiaolei Meng, Patrícia Dias, Bianca Ioana Moise, Haiyan Liu, Omer Cavus, Drew M. Nassal, Rengasayee Veeraraghavan, Przemysław Radwański
DOI: 10.1016/j.jacep.2025.12.033
Cited by: 1
References: 34

Abstract

Loss-of-function mutations in the SCN5A gene, which encodes for the predominant cardiac NaV isoform, NaV1.5, result in either deficiency in the channel expression or function. Impaired NaV1.5 expression and function underlie reduced peak Na+ current (INa) and result in ventricular conduction velocity slowing, predisposing the heart to conduction block and ventricular arrhythmias clinically associated with Brugada syndrome (BrS). Recently, a missense mutation in NaV1.5 selectivity filter (DEKA motif), K1419E (DEEA), has been identified in patients with BrS. Despite early characterization of mutations in selectivity filter of other NaV isoforms, little is known about the impact of DEEA on NaV1.5 function as well as on cardiac electrophysiology.

Fields of Study & Subjects

Cardiac electrophysiology and arrhythmias Cardiac Arrhythmias and Treatments Ion channel regulation and function

Publication details

Journal / source
JACC. Clinical electrophysiology
Publisher
Elsevier BV
Volume
12
Issue
5
Pages
945–956
Publication date
6 February 2026
Language
EN