Objective To investigate the effects of ropivaeaine and bupivacaine on voltage-gated potassium currents in cultures rat hippocampal neurons and the cellular basis of adverse effects of local anesthetics. Methods Hippocampal neurons were isolated from newborn Wistar rats and cultured and incubated for 8-12 days. The effects of ropivacaine and bupivacaine on delayed rectifier potassium current (IK) and transient outward potassium current (IA ) in cultured hippocampal neurons were recorded using whole cell patch clamp technique.Results (1) 100 μmol · L-1 and 1 000 μmol · L-1 ropivacaine reduced IK by 8.2% ± 2.0% and 12.3% ±3.0% (P>0.05); while 100 μmol·L-1 and 1 000 μmol· L-1 bupivacaine reduced IK by 24%) ±4% and 33% ±6% (P<0.05) respectively. (2) 0.1 μmol·L-1 ropivacaine and bupivacaine decreased the peak IA by 33% ±4% and 44% ±4% ( P < 0.001) ;1 μmol by 56% ± 4% and 72% ±6% (P < 0.001) ;10 μmol·L-1 by 86% ± 4% and 92% ± 5% ( P < 0.01) (3) The IC50 for ropivacaine and bupivacaine was (0.39 ± 0.19) μmol · L-1 and (0.14 ± 0.05) μmol · L -1 respectively. The inhibitory effects on IA were not voltage-dependent. Conclusion Ropivacaine and buaivacaine both significantly depress IA in rat hippocampal neurons. The potency of ropivacaine suppressing IA is significantly less than that of bupivacaine at the same concentration. Depression of IA in hippocampal neurons may contribute to the central nervous system toxicity of local anesthetics.