EP News: Basic and Translational

Abstract

Semaphorin-3A (SEMA3A)–encoded semaphorin is a chemorepellent that is analogous to hanatoxin, a K+ channel inhibitor. SEMA3A-knockout mice exhibit an abnormal electrocardiogram pattern and are prone to ventricular arrhythmias and sudden cardiac death. Boczek et al (Circ Res 2014;115:460, PMID 24963029) determined whether SEMA3A is a naturally occurring inhibitor of Kv4.3 (Ito) channels as well as its potential contribution to Brugada syndrome (BrS). SEMA3A selectively altered Kv4.3 in HEK293 cells by reducing peak current density without perturbing Kv4.3 cell-surface protein expression. Disruption of a toxin-binding domain on Kv4.3 was used to assess physical interactions between SEMA3A and Kv4.3 and revealed a direct binding interaction between these proteins. Mutational analysis of SEMA3A on 198 unrelated SCN5A-genotype–negative patients with BrS revealed 2 SEMA3A missense mutations that disrupted SEMA3A’s ability to inhibit Kv4.3 channels, resulting in a significant gain of Kv4.3 current compared with wild-type SEMA3A. The authors conclude that SEMA3A is a naturally occurring protein that selectively inhibits Kv4.3; thus, SEMA3A is a susceptibility gene for BrS. ErratumHeart RhythmVol. 12Issue 1PreviewIn the October 2014 issue of HeartRhythm (Vol 11, Issue 10, Page 1850), an EP News item referred to the first author of the article “Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome” (J Am Coll Cardiol 2014;64:66, PMID 24998131) as Dr. Barajas-Martínez. The first and corresponding author is Dr. Dan Hu. The Editors apologize for the misidentification. Full-Text PDF