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GABAA receptor-mediated inhibition depends on the maintenance of intracellular [C1] at low levels.The neuron specific K-C1 cotransporter KCC2 plays a pivotal role in neuronal inhibition by extruding Cl-and renders GABA and glycine action hyperpolarizing.However, KCC2 expression levels are reduced in various pathological conditions, including chronic pain, spinal cord injury, epilepsy and so on, with a resultant increased [C1-]i and a shift of GABA-mediated responses from hyperpolarizing to depolarizing.Previous work from our lab has shown that cyclothiazide (CTZ) induced seizure behavior in conscious rats and epileptiform activity in hippocampal neurons.In the present study, by using immunohistochemistry and western blot, we found the density labeling and the amount of KCC2 of the somatic membrane was reduced in the hippocampus 1d after CTZ induced acute epilepsy model.In cultured hippocampal neurons 48h after CTZ treatment, immunocytochemistry analyses by confocal and high resolution microscopy also revealed the down regulation of KCC2 signal at the plasma to cytoplasma.In addition, patch clamp results also demonstrated that CTZ that induced EGABA upshift and reduced Cl-extrusion ability in CA1 pyramidal neurons of inhippocampal slice, which was consistent with the result of molecular manipulated KCC2 down regulated cultured hippocampal neurons.Together, our data indicate that during CTZ induced epilepsy, plasma KCC2 was down regulated and function was inhibited.