The neuron specific K-Cl cotransporter KCC2 in adult plays an important role to maintain intracellular Cl-1 homeostasis, hence renders GABA receptor inhibitory properties.However, KCC2 expression levels are found to be reduced in various pathological conditions, including epilepsy.In current study, we analyzed KCC2 expression and function and its involvement in GABA receptor mediated inhibition change during acute seizure induction.By using cyclothiazide (CTZ) induced both in vivo and in vitro acute seizure model, we discovered that the hippocampal neuron somatic membrane KCC2 expression was down regulated, the GABA reversal potential (EGABA) was up-shifted and a profound reduction in Cl-extrusion ability.After molecular manipulation of KCC2 expression in cultured hippocampal neurons, CTZ treatment induced epileptic neurons was significantly reduced in association with KCC2 over expression, and KCC2 down regulated by shKCC2 resulted a EGABA up-shift but without effect on CTZ induction of epileptiform activities.In addition, furosemide, a KCC2 inhibitor, while applied continuously mimicked CTZ effect to cause the EGABA up-shift and facilitate the CTZ induced epileptiform activities.However, furosemide co-treated with CTZ prevented CTZ induced KCC2 down regulation from the somatic membrane and in turn rescued acute convulsant stimulation induced GABA inhibitory function reduction.In conclusion, our data suggest that KCC2 plays an important role in seizure induction and prevent KCC2 down regulation may be a novel target for anticonvulsant development.