A Novel Small Conductance Ca-activated K Channel Blocker from Oxyuranus scutellatus Taipan Venom

Taicatoxin, isolated from the venom of the Australian taipan snake Oxyuranus scutellatus, has been previously regarded as a specific blocker of high threshold Ca channels in heart. Here we show that taicatoxin (in contrast to a range of other Ca channel blockers) interacts with apamin-sensitive, small conductance, Caactivated potassium channels on both chromaffin cells and in the brain. Taicatoxin displays high affinity recognition of I-apamin acceptor-binding sites, present on rat synaptosomal membranes (Ki 5 1.45 6 0.22 nM) and also specifically blocks affinity-labeling of a 33-kDa I-apamin-binding polypeptide on rat brain membranes. Taicatoxin (50 nM) completely blocks apaminsensitive after-hyperpolarizing slow tail K currents generated in rat chromaffin cells (mean block 97 6 3%, n 5 12) while only partially reducing total voltage-dependent Ca currents (mean block 12 6 4%, n 5 6). In view of these findings, the use of taicatoxin as a specific ligand for Ca channels should now be reconsidered.