The delayed rectifier potassium current I(Ks) is important for repolarization of the cardiac action potential. In heart I(Ks) is a heteromeric channel composed of KCNQ1 (KvLQT1) and minK (KCNE1, IsK). Here we show that the KCNQ1/minK interaction is influenced by the expression system. Co-expression of KCNQ1 and minK in Xenopus oocytes resulted in potassium currents comparable to endogenous guinea pig cardiac I(Ks) in terms of temperature dependency and activation kinetics. In contrast, heterologous expression of I(Ks) in CHO cells revealed currents with a markedly different biophysical behavior. The sensitivity to the extracellular potassium concentration, temperature dependency and kinetics differ qualitatively. Potentially there is an endogenous component that affects I(Ks) which does not appear in all expression systems.