Buthus martensii Karsch (BmK) is widely used to cure nervous system diseases, such as pain, epilepsy, stroke, arthralgia and other diseases.However, these scorpion venom drugs used in clinic are highly toxic to mammalian with inevitable acute and chronic side effects.In our study, a kind of toxins which could induce the increase of intracellular [Ca2+]i were screened out from 96 peptides of BmK venom.BmK NT1, one of the most toxic neurotoxins, produced the neurotoxicity in vivo and in vitro.BmK NT1 could cause nervous system toxicity in mice, and also induces the death of primary cerebellar granule cells (CGCs).Trx is completely inhibited the neurotoxicity induced by BmK NT1, indicating the neurotoxicity is associated with the activation of VGSCs.Therefore, we characterized the mode of action of BmK NT1 on the VGSCs in primary cultured CGCs.BmK NT1 concentration-dependently delayed the fast inactivation and increased Na+ peak current amplitude in primary cultured CGCs.The EC50 value for BmK NT1 delaying the fast inactivation was 0.12 μM.The EC50 value for BmK NT1 increasing peak currents was 0.29 μM with a maximal response of 54.4% increment.For the current-voltage (Ⅰ-Ⅴ) relationship, BmK NT1 increased the peak currents at voltages ranging from-50 mV to +20 mV and shifted the activation voltage at maximum current from-15 mV to-20 mV.Collectively, the electrophysiological characteristics of BmK NT1 were similar to the mode of action of α-scorpion toxins.Combined with TTX could inhibit BmK NT1-induced neurotoxicity, we confirmed that BmK NT1-induced neurotoxicity is due to the activation of VGSCs.