Open AccessOverlapping Cardiac Phenotype Associated with a Familial Mutation in the Voltage Sensor of the KCNQ1 Channel
Author(s) -
Ulrike Henrion,
Sven Zumhagen,
Katja Steinke,
Nathalie StrutzSeebohm,
Birgit Stallmeyer,
Florian Läng,
Eric SchulzeBahr,
Guiscard Seebohm
Publication year - 2012
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000178470
Subject(s) - missense mutation , sinus bradycardia , mutation , long qt syndrome , voltage clamp , xenopus , medicine , biology , chemistry , membrane potential , genetics , microbiology and biotechnology , endocrinology , biophysics , bradycardia , gene , qt interval , heart rate , blood pressure
Cardiac action potential repolarisation is determined by K(+) currents including I(Ks). I(Ks) channels are heteromeric channels composed of KCNQ1 and KCNE E-subunits. Mutations in KCNQ1 are associated with sinus bradycardia, familial atrial fibrillation (fAF) and/or short QT syndrome as a result of gain-of-function, and long QT syndrome (LQTS) due to loss-of-function in the ventricles. Here, we report that the missense mutation R231C located in S4 voltage sensor domain is associated with a combined clinical phenotype of sinus bradycardia, fAF and LQTS. We aim to understand the molecular basis of the complex clinical phenotype.