Tityustoxin is a toxin found in the venom of scorpions from the subfamily Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.
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]
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]
The venom of Tityus serrulatus is the most potent of the toxins from the species. [3] Tityustoxin-1, TsTX-I is the most toxic protein among the neurotoxins in this venom, with an intravenous and intracisternal LD50 (mouse) of 76 ± 9 and 1.1 ± 0.3 μg/kg, respectively. The identification of TsTX-I as a potent component of T. serrulatus venom characterized it as the major and main neurotoxin from this venom. [1] Poisoning effects in man evoked by T. serrulatus venom are sialorrhea, lacrimation and rhinorrhea [3] and acute pancreatitis. [1] Catecholamines by the adrenal glands and postganglionic nerve terminals and Ach by ganglions and postganglionic nerve terminals are released when the poison strikes. Also other neurotransmitters are released by the whole venom and isolated toxins. [1] In rats, the Tityustoxin caused dramatic effects on the circulatory and respiratory systems, consisting of hypotension, tachypnea, hyperpnea, ataxic and gasping breathing. Following these initial effects, 5 or 10 μg of TsTX induced hypertension and hyperpnea. The largest dose produced apnea and death about 70 min later. [11]
The lung edema induced by TsTX is blocked by phenobarbital. [12] Rabbit anti-TsNTxP antibodies displayed cross-reactivity with the scorpion toxins and showed in vitro neutralizing capacity. Thus, this protein emerges as a strong candidate for the production of antiserum to be used in the treatment of scorpion stings. The nontoxic recombinant protein can induce a level of circulating antibodies sufficient to neutralize the toxic effects of Tityus toxins and is a good candidate for use in the production of a new generation of neutralizing polyclonal antibodies for clinical use. [13]
Calciseptine (CaS) is a natural neurotoxin isolated from the black mamba Dendroaspis p. polylepis venom. This toxin consists of 60 amino acids with four disulfide bonds. Calciseptine specifically blocks L-type calcium channels, but not other voltage-dependent Ca2+ channels such as N-type and T-type channels.
Phoneutria nigriventer toxin-3 is more commonly referred to as PhTx3.
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 much like pyrethroid insecticides do
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. Following injection into mice, it causes non-lethal writhing behaviour.
BmKAEP is a neurotoxin from the venom of the Manchurian scorpion (Mesobuthus martensii). It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.
Ikitoxin is a neurotoxin from the venom of the South African Spitting scorpion that targets voltage-sensitive sodium channels. It causes unprovoked jumps in mice following intracerebroventricular injections.
Butantoxin (BuTX) is a compound of the venom of three Brazilian and an Argentinean scorpion species of the genus Tityus. Butantoxin reversibly blocks the voltage-gated K+ channels Shaker B and Kv1.2, and the Ca2+-activated K+ channelsKCa 1.1 and KCa 3.1.
BotIT2 is a neurotoxin from the scorpion Buthus occitanus tunetanus, which modifies activation and slows down the deactivation of voltage gated sodium channels.
Bactridines are a group of six antibacterial peptides from the venom of the Tityusdiscrepans scorpion. They exclusively target sodium channels. Bactridines are unique in that this scorpion toxin acts on sodium channels of both bacteria and eukaryotes.
Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.
TsIV is a toxin from the venom of the Brazilian scorpion Tityus serrulatus which slows the inactivation of sodium channels.
Ts15 is produced by the Brazilian yellow scorpion Tityus serrulatus. It targets voltage-gated potassium channels, primarily the subtypes Kv1.2 and Kv1.3.
Tityustoxin peptide 2 (TsPep2) is a peptide isolated from the venom of the Tityus serrulatus. It belongs to a class of short peptides, together with Tityustoxin peptide 1 and Tityustoxin peptide 3.
Noxiustoxin (NTX) is a toxin from the venom of the Mexican scorpion Centruroides noxius Hoffmann which block voltage-dependent potassium channels and calcium-activated potassium channels.
Beta-mammal toxin Cn2, also known as Cn2 toxin, is a single chain β-scorpion neurotoxic peptide and the primary toxin in the venom of the Centruroides noxius Hoffmann scorpion. The toxin specifically targets mammalian Nav1.6 voltage-gated sodium channels (VGSC).
The Tst26 toxin is a voltage-gated potassium channel blocker present in the venom of Tityus stigmurus, a species of Brazilian scorpion. Tst26 selectively blocks Kv1.2 and Kv1.3 channels.
Ts8 is a neurotoxin present in the venom of the Brazilian yellow scorpion, Tityus serrulatus. Ts8 is a selective inhibitor of the voltage-gated potassium channel Kv4.2
Makatoxin-3 is an α-like scorpion neurotoxin found in the venom of Olivierus martensii. Makatoxin-3 both enhances the activation and slows down the inactivation of voltage-gated NaV1.7 channels, resulting in hyperexcitability of the neurons involved in pain perception.
Tb1 is a neurotoxin that is naturally found in the venom of the Brazilian scorpion Tityus bahiensis. Presumably by acting on voltage-gated sodium channels, it triggers excessive glutamate release, which can lead to both behavioral and electrographic epileptiform alterations, as well as neuronal injury.
Tityus stigmurus toxin 1 (Tst1) is a neurotoxin found in the venom of the Brazilian scorpion, Tityus stigmurus. It acts on voltage-gated sodium channels (Navs), altering opening and inactivation voltages, recovery from inactivation, and overall current flow.