Tityustoxin is a
toxin found in the
venom of
scorpions from the
subfamily
In biological classification, a subfamily (Latin: ', plural ') is an auxiliary (intermediate) taxonomic rank, next below family but more inclusive than genus. Standard nomenclature rules end subfamily botanical names with "-oideae", and zoologi ...
Tityinae. By binding to voltage-dependent
sodium ion channels and
potassium channels, they cause
sialorrhea,
lacrimation and
rhinorrhea.
Sources
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.
These species are found in Brazil (''
Tityus serrulatus
''Tityus serrulatus'', the Brazilian yellow scorpion, is a species of scorpion of the family Buthidae. It is native to Brazil, and its venom is extremely toxic. It is the most dangerous scorpion in South America and is responsible for the most f ...
,
T. bahiensis'' and ''
T. stigmurus'') and in Northern and Southern
Venezuela (''
T. discrepans'').
The venom of ''Tityus serrulatus'' is the most potent of these.
Chemistry
The crude venom of ''T. serrulatus'' contains different toxins. Some of the strongest derivates are the
neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
s tityustoxin and toxin Ts-g.
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.
Other types of venom are: TsTX-kα, a 37 amino acid, 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.
K+ channels blocking peptides are single chain
polypeptides of 30-40
amino acids with three
disulphide bridges
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
. The toxin with four disulphide bonds is from TsTX-IV. This contains 41 amino acid residues.
Targets
*
Na+ Channel affecting peptides: TsTX-γ and TsTX-I.
*
Ca2+ activated K+ Channel affecting peptides: TsTX-Kβ and
TsTX-IV (the latter has high affinity). TsTx-IV blocks Ca
2+ activated K
+ channels of high conductance.
Mode of action
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. Tityustoxin causes
cell depolarization, activating Na
+ channels and increasing the Na
+ uptake that can affect Ca
2+ uptake and can increase
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
(ACh) release from
cerebral cortical slices.
Na+ channels
The α-toxins bind to the subunit 3 of the sodium channel, slowing the inactivation and increasing peak current without changing time to peak.
This causes cell depolarization that opens
calcium channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels.
Comparison tables
The following tables e ...
s allowing the influx of Ca
2+, triggering ACh release.
Both the steady-state activation and inactivation curves are shifted to more negative potentials.
K+ channels
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. TsTX-Ka selectively blocks voltage-gated noninactivating (possibly delayed rectifier) K
+ channels in synaptosomes.
Toxicity
The venom of ''Tityus serrulatus'' is the most potent of the toxins from the species.
Tityustoxin-1, TsTX-I is the most toxic protein among the neurotoxins in this venom, with an intravenous and intracisternal (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.
Poisoning effects in man evoked by T. serrulatus venom are
sialorrhea,
lacrimation and
rhinorrhea and acute
pancreatitis.
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.
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
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
and
hyperpnea. The largest dose produced
apnea
Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ...
and death about 70 min later.
Treatment
The lung edema induced by TsTX is blocked by
phenobarbital. 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
Antiserum is a blood serum containing monoclonal or polyclonal antibodies that is used to spread passive immunity to many diseases via blood donation (plasmapheresis). For example, convalescent serum, passive antibody transfusion from a previous ...
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
Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body (whereas monoclonal antibodies come from a single cell lineage). They are a collection of immunoglobulin molecules that react against a ...
for
clinical use
A clinic (or outpatient clinic or ambulatory care clinic) is a health facility that is primarily focused on the care of outpatients. Clinics can be privately operated or publicly managed and funded. They typically cover the primary care needs ...
.
References
{{Reflist
Neurotoxins
Ion channel toxins