Congenital long QT syndrome is characterized by a prolongation of ventricular repolarization and recurrent episodes of life-threatening ventricular tachyarrhythmias, often leading to Ridden death. We previously identified a missense mutation F275S located within the S5 transmembrane domain of the KCNQ1 ion channel in a Chinese family with long QT syndrome. We used oocyte expression of the KCNQ1 poly-peptide to study the effects of the F275S mutation oil channel properties. Expression of the F275 mutant, or co-expression with the wild-type S275 polypeptide, significantly decreased channel current amplitudes. Moreover, the F275S substitution decreased the rates of channel activation and deactivation. In transfected HEK293 cells fluorescence microscopy revealed that the F275S mutation perturbed the sub-cellular localization of the ion channel. These results indicate that the F275S KCNQ1 Mutation leads to impaired polypeptide trafficking that in turn leads to reduction of channel loll currents and altered gating kinetics. (C) 2009 Elsevier Inc. All rights reserved.