Martentoxin as a 37 residues peptidyl toxin was capable of blocking large-conductance Ca2+-activated K+ (BK) channels in adrenal medulla chromaffin cells.The present study investigated the pharmacological discrimination of martentoxin on BK channels subtypes and implicated the physiological function of neuronal BK channels (c+β4).The results showed that the iberiotoxin-insensitive BK channels (α+β4) could be potemly blocked by martentoxin (IC50 =~80nM).In contrast,the iberiotoxin-sensitive BK channel (only α) showed a low sensitivity to martentoxin.The inhibitory effect of martentoxin on BK channels (α+β4) appears with a novel interaction mode,including Ca2+ dependence and two possible interaction sites:one for trapping and the other for inhibition.Furthermore,in vivo experimems also suggested that the inhibition of BK channels (α+β4) by martentoxin would induce exacerbated abno-mal discharges,which indicated a braking role of BK channels (α+β4) in spontaneous bursting activity.