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 f rom the venom of the green mamba, Dendroaspis angusticeps: a neurotoxin tha t enhances acetylcholine release at neuromuscular junctions. Naunya-Schmied ebergs Arch. Pharmacol. 312, 1-6.). Subsequently, a family of related prote ins was found in mamba venoms and shown to be homologous to Kunitz-type ser ine protease inhibitors, such as aprotinin. The dendrotoxins contain 57-60 amino acid residues cross-linked by three disulphide bridges. The dendrotox ins have little or no anti-protease activity, but they were demonstrated to block particular subtypes of voltage-dependent potassium channels in neuro ns. Studies with cloned K+ channels indicate that alpha-dendrotoxin from gr een mamba Dendroaspis angusticeps blocks Kv1.1, Kv1.2 and Kv1.6 channels in the nanomolar range, whereas toxin K from the black mamba Dendroaspis poly lepis preferentially blocks Kv1.1 channels. Structural analogues of dendrot oxins have helped to define the molecular recognition properties of differe nt types of K+ channels, and radiolabelled dendrotoxins have also been usef ul in helping to discover toxins from other sources that bind to K+ channel s. Because dendrotoxins are useful markers of subtypes of K+ channels in vi vo, dendrotoxins have become widely used as probes for studying the functio n of K+ channels in physiology and pathophysiology. (C) 2000 Elsevier Scien ce Ltd. All rights reserved.