Dendrotoxin

Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes (Dendroaspis) that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions.

In this way, dendrotoxins prolong the duration of action potentials and increase acetylcholine release at the neuromuscular junction, which may result in muscle hyperexcitability and convulsive symptoms.

Most of the positively charged amino acid residues of dendrotoxins are located in the lower part of the structure, creating a cationic domain on one side of the protein.

It is generally believed (though not proven) that a dendrotoxin molecules bind to anionic sites near the extracellular surface of the channel and physically occlude the pore, thereby preventing ion conductance.

Many studies have attempted to identify which amino acid residues are important for binding activity of dendrotoxins to their potassium channel targets.

Similar results have been shown with dendrotoxin-K using site-directed mutagenesis to substitute positively charged lysine and arginine residues to neutral alanines.

These results, along with many others, have implicated that the positively charged lysines in the N-terminal half, particularly Lys5 in the 310-helix, play a very important role in the dendrotoxin binding to their potassium channel targets.

Therefore, voltage-gated potassium channels are targets for a wide range of potent biological toxins from such organisms as snakes, scorpions, sea anemones, and cone snails.

Because of their potency and selectivity for different subtypes of potassium channels, dendrotoxins have become useful as molecular probes for the structural and functional study of these proteins.