Objective:To study the effect of scorpion polypeptide purified from Buthus martensi Karsch(BmK) venom on membrane potential of PC12 cells and its correlation with sodium channel. Methods:PC12 cells were labeled with DiBAC4(3). Laser scanning confocal microscope was used to monitor the changes of membrane potential at real time on these cells that were treated with different concentrations of the scorpion polypeptide. The effect of sodium channel blocker TTX(tetrodotoxin) on the changes was also observed. Results:Membrane potential depolarization induced by the scorpion polypeptide peaked at 3 min and became stabilized after 5 min of the treatment. After comparing to fluorescence intensity without treatment,the normalized fluorescence intensity was determined to be 1.375 ± 0.048,1.504 ± 0.034 and 1.839 ± 0.022 in cells that were treated with 10,20,40 μg/ml scorpion polypeptide,respectively. These numbers are significantly lower than those from untreated control cells(P < 0.01). When PC12 cells were co-incubated with 1 μmol/L TTX for 20 min,then treated with 40 μg/ml scorpion polypeptide,the intensity changed to 1.035 ± 0.028,which was similar to that of the control(P > 0.05). This indicated that the effect of scorpion polypeptide could be completely inhibited by TTX. Conclusion:The scorpion polypeptide induced membrane depolarization of PC12 cells in a concentration-dependent manner,suggesting that the sodium channel should be involved.