Objective:To explore the effects of gp120 on TEA sensitive K+ currents and the role of the currents in gp120 induced neuronal apoptosis. Methods: Hippocampal neurons were harvest from 18-day-old embryonic rats and divided into two groups: the control and the gp120 treated group. The outward delayed K+ currents were recorded by performing the whole cell patch clamp, subsequently the cell viability as well as neuron apoptosis were evaluated by MTT and TUNEL assay,respectively. Moreover, the protein expression of Kv2.1, a subtype of TEA sensitive K+ channel, was detected by Western blot. Results: Gp120 significantly increased the outward K+ currents in a dose-dependent manner, and the TEA sensitive K+ currents were participated in K+ currents increment mediated by gp120. The MTT and TUNEL results revealed that gp120 substantially decreased the cell viability and enhanced the cell apoptosis, while the K+ antagonist TEA was effectively decreased gp120 induced cell damage. Moreover, the expression and contribution of Kv2.1 on TEA sensitive K+ currents was significantly up-regulated by gp120. And the specific blocker, GxTX-1E, was used for evaluating the role of Kv2.1 in TEA sensitive K+ currents. Conclusion: TEA sensitive K+ currents were involved in gp120 induced neuronal damage, and the subtype Kv2.1, which was up-regulated by gp120, might exert effects on gp120 induced cell damage.