Ikitoxin
Category	Ion channel toxin, Neurotoxin Neurotoxin A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
Species	Parabuthus transvaalicus Parabuthus transvaalicus Parabuthus transvaalicus is a species of scorpion from southern Africa. It is also known as "Dark Scorpion".-Description:P. transvaalicus grows to a length of , and is dark brown or black in colour. Its pincers are thin, but its tail is thickened, with the sting segment being as wide as the rest of...
Target	voltage-gated sodium channel
Symptoms	Unprovoked jumps
Sequence length	58 AA

Ikitoxin is a neurotoxin from the venom of the South African Spitting scorpion

Parabuthus transvaalicus

Parabuthus transvaalicus is a species of scorpion from southern Africa. It is also known as "Dark Scorpion".-Description:P. transvaalicus grows to a length of , and is dark brown or black in colour. Its pincers are thin, but its tail is thickened, with the sting segment being as wide as the rest of...

 (Parabuthus transvaalicus) that targets voltage-sensitive sodium channels. It causes unprovoked jumps in mice following intracerebroventricular injections.

Source

Ikitoxin is one of the many components that can be isolated from the venom of the South African Spitting scorpion. Other peptide toxins found in the venom include birtoxin

Birtoxin

Birtoxin is a neurotoxin from the venom of the South African Spitting scorpion . By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing.-Source:...

, which is moderately toxic but very abundant, dortoxin

Dortoxin

Dortoxin is a lethal peptide toxin which is secreted by the South African spitting scorpion Parabuthus transvaalicus. Injection of pure dortoxin in mice leads to hyperactivity that lasts until death.-Source:...

, a lethal peptide, bestoxin

Bestoxin

Bestoxin is a neurotoxin from the venom of the South African spitting scorpion Parabuthus transvaalicus. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing...

, which causes writhing in mice, and altitoxin

Altitoxin

Altitoxin is a neurotoxin found in the South African scorpion Parabuthus transvaalicus. Injection of altitoxin in mice leads to akinesia, depression and death.-Source:...

, a highly depressant peptide.

Chemistry

Ikitoxin is a member of the birtoxin family of peptide neurotoxins that target sodium channels. Although identified as a long chain neurotoxin, which usually have 64-70 residues with four disulfide bridges, ikitoxin, like birtoxin, has a smaller size (58 residues) with only three disulfide bridges. Ikitoxin differs from birtoxin by a single amino acid: from glycine to glutamic acid at position 23, consistent with an apparent mass difference of 72 Da between the two peptides.

Mode of action

Both ikitoxin and birtoxin are beta toxins, which bind to and trap the voltage sensor of the channel at side 4. The binding of ikitoxin lowers the voltage threshold of sodium channels and produce a reduction in the current amplitude. As a result of the change in their activation properties, sodium channels will open at smaller depolarizations, resulting in increased excitability.

Toxicity

Ikitoxin diffs from birtoxin by only a single residue, but has a markedly reduced biological activity. In mice experiments, intracerebroventricular administration of ikitoxin induced unprovoked jumps. These jumps were observed at a concentration that was 1000-fold higher than in the case of birtoxin, and their onset was much slower. Another difference between these toxins is that birtoxin produced convulsions, tremors, increased ventilation and, subsequently, death. Injection of up to 4 μg of ikitoxin in mice was not lethal. Ikitoxin seems to affect only mammals.

Treatment

Ikitoxin is one of many neurotoxic polypeptide components in the venom of the South African Spitting scorpion. It has a birtoxin-like structure. Antibodies against the N-terminus of the birtoxin protein structure can neutralize the venom of the South African spitting scorpion, and such antibodies may be useful clinically to treat envenomation.