OBJECTIVE Methamphetamine (Meth) abusing represents a major public health problem worldwide.Meth has long been known to induce neurotoxicity.However, the mechanism is still unclear.The aim of the present study was to identify the specific targets mediated by Meth in microglia.Growing evidences indicated that the voltage-gated potassium channels (Kv) were participated in neuronal damage and microglia functionality.Therefore, in present study, we explored the effects of Kv1.3 in microglia damage mediated by Meth.METHODS Microglial cell from 18-day-old embryonic rats were divided into 4 groups treat with methamphetamine(0, 100,300, 1000 μmol·L-1).CCK8 assay was applied to indicate cell viability.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptotic cells.Immunohistochemistry was used to identify Microglial cell.Real-time PCR was applied to observe the expressions of IL-6 and iNOS.Western blot assay were performed to determine the expressions of Kv1.3 and Kv1.5 in Microglial cell.RESULTS Our study showed that Meth substantially decreased the cell viability in a dose dependent manner, while the Kv blocker, TEA, 4-AP and Kv1.3 specific antagonist margatoxin (MgTx), preventing against the damage mediated by Meth.Accordingly, the association between cell damage and Kv1.3 expression was discussed and the results revealed that treatment of microglia with Meth increased Kv1.3 mRNA expression.In parallel, western-blot study indicated an up-regulation of Kv1.3 protein, which was partly blocked by MgTx.However, Kv1.5, another K + channel in microglia, was not obviously affected by Meth treatment.Meth also stimulated a significant increment of IL-6 mRNA expression, and this process can be partly blocked by MgTx.CONCLUSION These results together not only revealed the effects of Kv1.3 in Meth induced microglia damage, but also suggested a potential target for the development of therapeutic strategies for Meth abuse.