Referenced in: none

Automatically associated channels: Kv1.4 , Kv11.1 , Kv3.1 , Kv4.3 , Kv8.2

Title: KCNE3 mutation V17M identified in a patient with lone atrial fibrillation.

Authors: Alicia Lundby, Lasse Steen Ravn, Jesper Hastrup Svendsen, Stig Hauns, Søren-Peter Olesen, Nicole Schmitt

Journal, date & volume: Cell. Physiol. Biochem., 2008 , 21, 47-54

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18209471

Abstract
Atrial fibrillation (AF) is the most common cardiac rhythm disorder with a lifetime risk for development of 25% for people aged 40 or older. In this study we aim for the functional assessment of a mutation in KCNE3 identified in a proband with early-onset lone AF.Screening of genomic DNA from the proband led to identification of a KCNE3 V17M missense mutation. We heterologously expressed the accessory channel subunit in Xenopus laevis oocytes together with its known interacting potassium channel alpha-subunits. Further, we applied RT-PCR on human total RNA from left and right atria and ventricle.Electrophysiological recordings revealed an increased activity of Kv4.3/KCNE3 and Kv11.1/KCNE3 generated currents by the mutation, thereby conferring susceptibility of mutation carriers to faster cardiac action potential repolarization and thus vulnerability to re-entrant wavelets in the atria and thereby AF.Here we report a novel mutation in KCNE3 identified in a proband with early-onset lone AF possibly leading to gain-of-function of several cardiac currents. We suggest abnormalities in the KCNE3 gene as a potential genetic risk factor for initiation and/or maintenance of AF.