Channelpedia

PubMed 17675083


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv11.1 , Kv7.1 , Nav1.5



Title: Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction.

Authors: Dan Hu, Sami Viskin, Antonio Oliva, Tabitha Carrier, Jonathan M Cordeiro, Hector Barajas-Martinez, Yuesheng Wu, Elena Burashnikov, Serge Sicouri, Ramon Brugada, Rafael Rosso, Alejandra Guerchicoff, Guido D Pollevick, Charles Antzelevitch

Journal, date & volume: , 2007 Aug , 4, 1072-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17675083


Abstract
Ventricular tachycardia (VT) and ventricular fibrillation (VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) both have been linked to phase 2 reentry.Given the mechanistic similarities in arrhythmogenesis, the purpose of this study was to examine the contribution of SCN5A mutations to VT/VF complicating AMI.Nineteen consecutive patients developing VF during AMI were enrolled in the study. Wild-type (WT) and mutant SCN5A genes were coexpressed with SCN1B in TSA201 cells and studied using whole-cell patch clamp techniques.Among the cohort of 19 patients, one missense mutation (G400A) in SCN5A was detected in a conserved region. An H558R polymorphism was detected on the same allele. Unlike the other 18 patients, who each developed 1-2 VF episodes during AMI, the mutation carrier developed six episodes of VT/VF within the first 12 hours. All VT/VF episodes were associated with ST-segment changes and were initiated by short-coupled extrasystoles. Flecainide and adenosine challenge performed to unmask Brugada and long QT syndromes both were negative. Peak G400A and G400A+H558R current were 70.7% and 88.4% less than WT current at -35 mV (P </=.001). G400A current decay was accelerated and steady-state inactivation was shifted -6.39 mV (V(1/2) = -98.9 +/- 0.1 mV vs -92.5 +/- 0.1 mV, P </=.001). No mutations were detected in KCNH2, KCNQ1, KCNE1, or KCNE2 in the G400A patient.We describe the first sodium channel mutation to be associated with the development of an arrhythmic storm during acute ischemia. These findings suggest that a loss of function in SCN5A may predispose to ischemia-induced arrhythmic storm.