Martentoxin as a 37 residues peptide purified from the venom of Chinese scorpion Buthus martensi Karch (BmK) was capable of blocking large-conductance Ca2+-activated K+ (BK) channels in adrenal medulla chromaffin cells with a great preference.In the present study,the pharmacological effect of martentoxin on glioma BK channels (gBK),which was a splice variant of hslo α subunits,was investigated through the electrophysiological approach.The results revealed that gBK were blocked by martentoxin in the absence of cytosolic Ca2+-The inhibitory effect of martentoxin on gBK was conversed to an enhancive effect in the presence of cytosolic Ca2+.The enhancement occurred without voltage-dependence but dose-dependence.Furthermore,martentoxin could decrease the inhibitory effect of iberiotoxin or tetrabutylammonium chloride on gBK with free Ca2+ in the cytosol.Ca2+ imaging showed that martentoxin could not evoke the oscillation of cytoplasmic Ca2+ concentration and excluded the possible influence of martentoxin on cytosolic Ca2+.Therefore,the results suggested that the pharmacological effect of martentoxin on gBK was decided by cytosolic Ca2+ and the interaction site of gBK for martentoxin might be different from that for Ibtx or tetrabutylammonium chloride.The present study shed light on a novel mode for the interaction between neurotoxins and K+ channels and may provide a potential design for the BK channel-specific tool.