Pompilidotoxin

Alpha-, and beta-pompilidotoxin(PMTX) inhibits sodium channels inactivation or strengthen the sodium channel activation. This results in summation of postsynaptic potentials. Beta-PMTX is 5-fold more potent than alpha-PTMX.

Etymology

Pompilidotoxin is named after the pompilidae wasp family (commonly called spiderwasps).

Source

This toxin is extracted from the venom of the spiderwasp Anoplius samariensis.

Chemistry

Structure Alpha-PMTX has 13 amino acid residues and the sequence of Arg-Ile-Lys-Ile-Gly-Leu-Phe-Gln-Asp-Leu-Ser-Lys-Leu-NH2. Replacement of the lysine residue at 12 position of alpha-PMTX with arginine, results in beta-PMTX.

Homology A-PMTX has no structural homology with other toxins. It lacks disulphide bonds which are known to be present in other toxins as sea anemone toxins or scorpion toxins.

FamiliyPMTX is a neurotoxin, which shows no homology with other well known toxins.

Target

PMTX possibly binds to elements of the neurotoxin receptor site 3 on the extracellular surface of the sodium channel.

Affinity

There are two PMTX toxins known which can be found in the venom of species of the Pompilidae family, respectively alpha and beta PMTX. This last toxin can also be made by chemical modification of a-PMTX by replacement of arginine at position 12 into lysine. This modification causes a five times stronger potency then that of a-PMTX.

Mode of action

Whole-cell recordings from rat trigeminal ganglion neurons revealed that PMTXs slowed the inactivation of sodium currents. These findings suggest that a-PMTX may act by influencing the activation or inactivation of Na channels, but differ from previously known neurotoxins.

Toxicity

The clinical consequences of PMTX’s for human beings remain unknown.Although spiders show immediately paralysation after injection of 1-2 µl of PMTX. The amount of PMTX protein from a wasp was determined to be approximately 60 µg.

Therapeutic use

Because PMTXs discriminate between neuronal and cardiac Na+ channels, derivatives of the toxin may be advantageous to therapeutic use without affecting heart muscle. Furthermore, the novel toxin affect differently in the central neurons, suggesting existence of PMTX-sensitive and PMTX-insensitive Na+ channels. When there will be a disability of PMTX-sensitive sodium channels in human the toxin may serve as a valuable tool for regulation of these channel.

References