The plateau phase of the ventricular action potential is the result of balanced Ca²⁺ influx and K⁺ efflux. Under beta-adrenergic stimulation the slowly activating component of the human cardiac delayed rectifier K⁺ current I_Ks provides the mayor repolarising component. I_Ks channels are generated by heteromeric channels KCNQ1/KCNE1. Mutations in the voltage sensor S4 of KCNQ1 are associated with long-QT syndrome 1. Here, we study the effects of the mutations S225L, I235N and L239P located in S4. The respective channels were expressed in Xenopus oocytes and analyzed by voltage clamp. All mutants shifted the voltage dependence of activation to the right and reduced voltage dependence of deactivation kinetics whereas activation kinetics were differently affected in homomeric mutant channels compared to wild type KCNQ1. All three mutations reduced KCNQ1/KCNE1 channel currents in a dominant-negative manner when coexpressed with wt subunits. According to a mathematical ventricular action potential model the mutant S225L and possibly I235N favored the triggering of early after depolarisations and potentially fatal torsade de pointes arrhythmia during increase of I_CaL associated with beta-adrenergic stimulation under acute stress.