Tityustoxin

Scorpions are distributed among six families. Only those of the family Buthidae are dangerous to humans. Within this family, the subfamily Tityinae cause the most scorpion poisoning in humans.^[1] These species are found in Brazil (Tityus serrulatus, T. bahiensis and T. stigmurus) and in Northern and Southern Venezuela (T. discrepans).^[2] The venom of Tityus serrulatus is the most potent of these.^[1]

The crude venom of T. serrulatus contains different toxins. Some of the strongest derivates are the neurotoxins tityustoxin and toxin Ts-g.^[3] Two types of toxins are considered to be responsible for the main toxic effect: toxin gamma (a β-type toxin) and tityustoxin (TsTX, an α-type toxin), both with a specific affinity to the sodium channel.^[4] Other types of venom are: TsTX-kα, a 37 amino acid,^[5] toxin gamma (TsTX-γ and TsTX-I) with 61 amino acid residues is the major neurotoxin of this venom. TsTX-Kβ has a longer chain.^[2] K+ channels blocking peptides are single chain polypeptides of 30-40 amino acids with three disulphide bridges.^[6] The toxin with four disulphide bonds is from TsTX-IV. This contains 41 amino acid residues.^[2]

• Na⁺ Channel affecting peptides: TsTX-γ and TsTX-I.^[2]
• Ca²⁺ activated K⁺ Channel affecting peptides: TsTX-Kβ and TsTX-IV (the latter has high affinity). TsTx-IV blocks Ca²⁺ activated K⁺ channels of high conductance.^[2]

Two types of toxin are interesting: α-Scorpion toxins bind at site 3 of Na1 channels, causing a slowing of their inactivation. β-Scorpion toxins bind at site 4, shifting the activation of Na1 currents (INa) toward more negative potentials.^[7] Tityustoxin causes cell depolarization, activating Na⁺ channels and increasing the Na⁺ uptake that can affect Ca²⁺ uptake and can increase acetylcholine (ACh) release from cerebral cortical slices.^[8]

The α-toxins bind to the subunit 3 of the sodium channel, slowing the inactivation and increasing peak current without changing time to peak.^[4] This causes cell depolarization that opens calcium channels allowing the influx of Ca²⁺, triggering ACh release.^[8] Both the steady-state activation and inactivation curves are shifted to more negative potentials.^[4]

TsTX-I, Ts1 or toxin gamma is a β-type toxin that binds to receptor site 4 and shift the voltage dependence of the sodium channel activation to more negative potentials.^[9] TsTX-Ka selectively blocks voltage-gated noninactivating (possibly delayed rectifier) K⁺ channels in synaptosomes.^[10]