＜正＞ Background Atrial fibrillation is a common arrhythmia with multi-factorial pathogenesis.Recently,a single nucleotidepolymorphism （G/T） at position 1057 in the KCNE4 gene,resulting in a glutamic acid （Glu,E）/aspartic acid （Asp,D）substitution at position 145 of the KCNE4 peptide,was found in our laboratory to be associated with idiopathic atrialfibrillation （atrial fibrillation more frequent with KCNE4 145D）.However,the functional effect of the KCNE4 145E/Dpolymorphism is still unknown.Methods We constructed KCNE4 （145E/D） expression plasmids and transiently co-transfected them with the KCNQ1gene into Chinese hamster ovary-K1 cells and performed whole-cell patch-clamping recording to identify the possiblefunctional consequences of the single nucleotide polymorphism.Quantitative data were analyzed by Student’s t test.Probability values less than 0.05 were considered statistically significant.Results A slowly activating,non-inactivating voltage-dependent current （（24.0±2.9） pA/pF,at +60 mV）) could berecorded in the cells transfected with KCNQ1 alone.Co-expression of wild type KCNE4 inhibited the KCNQ1 current（（7.3±1.1） pA/pF）).By contrast,co-expression of KCNE4 （145D） augment the KCNQ1 current （（42.9±3.7） pA/pF）).TheV1/2 of activation for the KCNQ1/KCNE4 （145D） current was shifted significantly towards the depolarizing potentialcompared to that for the KCNQ1 current （（-2.3±0.2） mv vs （-13.0±1.5） mv,P＜0.01）) without changing the slopefactork.Furthermore,KCNE4 （145D） also affected the activation and deactivation kinetics of KCNQ1 channels.Conclusion We provide experimental evidence that the KCNE4 （145E/D） polymorphism exerts the effect of"gain offunction"on the KCNQ1 channel.It may underlie the genetic mechanism of atrial fibrillation.Further studies on thefunctional association between IKs and KCNE4 （145D） polymorphism in cardiac myocytes are suggested.
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