Abstract: AimTo study the effects of 17β-estradiol on Kv2.1 potassium channel current and delayed rectifier potassium current (I_K) in cultured rat hippocampal neurons. MethodsThe effects of 17β-estradiol on Kv2.1 channel current and I_K in cultured rat hippocampal neurons were observed using the whole cell patch clamp techniques. Results17β-Estradiol was shown to reduce the amplitude of Kv2.1 current and I_K in concentration-dependent manners. The IC₅₀s of 17β-estradiol blocking Kv2.1 and I_K were 2.4 and 4.0 μmol·L^-1, respectively. 17β-Estradiol (3 μmol·l^-1) significantly shifted the steady-state activation and inactivation curves of Kv2.1 current to negative potentials. However, it only produced the shift of the steady-state activation curve of I_K to the negative potential without effect on the steady-state inactivation of I_K. Conclusion17β-Estradiol inhibits Kv2.1 and I_K of hippocampus at similar level. The inhibition of 17β-estradiol on I_K current may be partially via blocking Kv2.1current.