Twenty years of dendrotoxins

Dendrotoxins are small proteins that were isolated 20 years ago from mamba ( Dendroaspis) snake venoms (Harvey, A.L., Karlsson, E., 1980. Dendrotoxin from the venom of the green mamba, Dendroaspis angusticeps: a neurotoxin that enhances acetylcholine release at neuromuscular junctions. Naunyn-Schmiedebergs Arch. Pharmacol. 312, 1–6.). Subsequently, a family of related proteins was found in mamba venoms and shown to be homologous to Kunitz-type serine protease inhibitors, such as aprotinin. The dendrotoxins contain 57–60 amino acid residues cross-linked by three disulphide bridges. The dendrotoxins have little or no anti-protease activity, but they were demonstrated to block particular subtypes of voltage-dependent potassium channels in neurons. Studies with cloned K + channels indicate that α-dendrotoxin from green mamba Dendroaspis angusticeps blocks Kv1.1, Kv1.2 and Kv1.6 channels in the nanomolar range, whereas toxin K from the black mamba Dendroaspis polylepis preferentially blocks Kv1.1 channels. Structural analogues of dendrotoxins have helped to define the molecular recognition properties of different types of K + channels, and radiolabelled dendrotoxins have also been useful in helping to discover toxins from other sources that bind to K + channels. Because dendrotoxins are useful markers of subtypes of K + channels in vivo, dendrotoxins have become widely used as probes for studying the function of K + channels in physiology and pathophysiology.