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Dendrotoxins: Powerful Blockers of Voltage-Gated K+ Channels

By Dovrat Brass, M.Sc., B. Pharm.

Dendrotoxins are a family of 7 kDa. homologous polypeptides isolated from both green and black mamba venoms (Dendroaspis sp.)1-3. They contain 57-61 amino acid residues in a single chain, crosslinked by three disulfide bridges. Several Dendrotoxins have been isolated and their amino acid sequences completely (see Table 1) , while β- and γ-Dendrotoxin have only been partially sequenced1-4.

Dendrotoxins were first discovered to facilitate the release of acetylcholine at the neuromuscular junction4,5. Later discoveries demonstrated their ability to selectively block some voltage-dependent K+ channels in nerve endings with high affinity2,5.

Dendrotoxins are potent inducers of epilepsy and convulsions in the central nervous system and have been shown to produce behavioral, electrocortical and neuropathological effects when injected into various brain regions6-12.

Thanks to extensive research developments over the last twenty years in electrophysiology, molecular biology and structure-activity relationships analysis techniques, dendrotoxins are used in both in vivo and in vitro trials, as pharmacological tools for isolating and exploring the function and the molecular recognition properties of different types of K+ channels proteins in the brain13,14 and peripheral neurons6,15.

Table 1. Amino Acid Sequence of Dendrotoxins
The dashes or x indicate unidentified residues. Lower case letters indicate some uncertainty.

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