AIM The purpose of this study was to study the influence of KCNE4 on potassium ion channel KCNQ 1 and HERG.Method We constructed KCNE4 expression plamids and performed the whole-cell patch-clamp recording on cells co-transfected with KCNQ1 or HERG to identify potential functional consequences.immunocytochemistry was used to study protein co-localization.Results KCNQ1-expressing ceils showed a slowly activating, non-inactivating voltage-dependent current (current density 24 ± 2.9pA/pF recorded at +60mV).The presence of KCNE4 resulted in a dramatic decrease of the KCNQ1 current and produced almost undetectable currents between-80mV to +60mV.In KCNQ1+KCNE4 expressing cells, the current density was 7.3±1.1pA/pF.Subcellular localization study showed the same plasma membrane fluorescence pattern of KCN Q1 when co-expressed with KCNE4.It implied KCNE4 had no effect on the protein trafficking and localization ofKCNQ1.KCNE4 had no effects on the HERG current.Conclusion Our data suggest that KCNE4 dramatically decreased KCNQ 1 current density at physiologically relevant potentials and showed an inhibitory property on KCNQ1 channel.KCNE4 had no effect on HERG channel.