Background: Atrial fibrillation (AF) is the most common cardiac rhythm disorder with a lifetime risk for development of 25 % for people aged 40 or older [1]. In this study we aim for the functional assessment of a mutation in KCNE3 identified in a proband with early-onset lone AF. Methods: 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 α-subunits. Further, we applied RT-PCR on human total RNA from left and right atria and ventricle. Results: 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. Conclusion: 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.

Keywords:
Atrial fibrillation, KCNE3, KCNQ1, KCNQ4, Kv7.1, Kv7.4, hERG, Kv11.1, Kv1.5, Kv4.3
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© 2008 S. Karger AG, Basel
2008
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