Verrucotoxin (VTX) is a lethal venom produced by the dorsal fins of ''

Synanceia verrucosa ''Synanceia verrucosa'', the reef stonefish or just stonefish, is a species of venomous, marine ray-finned fish, a stonefish belonging to the subfamily Synanceiinae which is classified as being within the family Scorpaenidae, the scorpionfish ...

''. This species of reef stonefish is connected to the family ''

Synanceiidae Synanceiinae is a subfamily of venomous ray-finned fishes, waspfishes, which is classified as part of the family Scorpaenidae, the scorpionfishes and their relatives. These fishes are found in the Indo-Pacific oceans. They are primarily marin ...

''. The venom of this species of stonefish is a

tetrameric A tetramer () (''tetra-'', "four" + ''-mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti( ...

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

with cardiovascular and

cytolytic Cytolysis, or osmotic lysis, occurs when a cell bursts due to an osmotic imbalance that has caused excess water to diffuse into the cell. Water can enter the cell by diffusion through the cell membrane or through selective membrane channels ...

effects.

Structure

The structure of verrucotoxin is a tetrameric protein with a molecular weight of 322 KDa; the protein consists of two parts of an alpha subunit (83 KDa) and two parts of a beta subunit (78 KDa). Verrucotoxin shares a total of 96% homology to the closely related venom stonustoxin beta subunit. Stonustoxin is the venom produced from ''

Synanceia horrida ''Synanceia horrida'', the estuarine stonefish, hollow-cheek stonefish, horrid stonefish, rough stonefish or true stonefish, is a species of venomous, marine ray-finned fish, a stonefish belonging to the subfamily Synanceiinae which is classifi ...

''.

Function and mechanism

Verrucotoxin has been studied to interact with both calcium ion channels and potassium ATP channels. The

calcium ion 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 ex ...

is modulated by the activation of the ꞵ-adrenoceptors when verrucotoxin binds. There are three subunits of ꞵ-adrenoceptors, ꞵ1, ꞵ2, and ꞵ3, but only ꞵ2-adrenoceptors are responsible for the activation of the cyclic adenosine monophosphate (cAMP)- protein kinase (PKA) pathway. The cAMP will phosphorylate muscle regulatory proteins and modulate intercellular calcium concentrations. It is through this method that verrucotoxin operates the concentrations of calcium in the cell. Verrucotoxin is a concentration-dependent toxin to the concentration of calcium ions; the presence of verrucotoxin can increase the calcium concentration three times the standard intercellular concentration. Additionally, verrucotoxin has been observed to cause a reversible prolonged action potential duration with zero change in resting membrane potential from ventricular myocytes in guinea pigs. The second method verrucotoxin disrupts cells are through potassium ion channels, particularly the potassium adenosine triphosphate (KATP) pathway. The potassium ATP channel operates by pumping potassium ions out of the intercellular membrane.{{Cite journal, last1=Tinker, first1=Andrew, last2=Aziz, first2=Qadeer, last3=Thomas, first3=Alison, date=January 2014, title=The role of ATP-sensitive potassium channels in cellular function and protection in the cardiovascular system, journal=British Journal of Pharmacology, volume=171, issue=1, pages=12–23, doi=10.1111/bph.12407, issn=0007-1188, pmc=3874693, pmid=24102106 It’s capable of doing so by

phosphorylating In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...

the channel with Adenosine Triphosphate (ATP). Verrucotoxin is able to inhibit the operation of the potassium ATP through the activation of muscarinic M3 receptor-

protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...

(PKC). It is the activation of the PKC that will inhibit the potassium ion channel. The PKC is presumably phosphorylating the KATP channel instead of ATP.

Adverse effects

The stonefish, ''

'', has a diverse set of toxins that disrupts basic human ability. When injected with the toxins found in the dorsal fins of the fish, individuals will suffer from skeletal muscle paralysis, extreme pain, seizures,

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...

respiratory arrest Respiratory arrest is a sickness caused by apnea (cessation of breathing) or respiratory dysfunction severe enough it will not sustain the body (such as agonal breathing). Prolonged apnea refers to a patient who has stopped breathing for a long p ...

, and damage to the

cardiovascular system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

. Verrucotoxin has been studied to be the cause of cardiovascular system damage, convulsions, seizures, and paralysis. For the cardiovascular system damage, it is caused by the sudden change in the intercellular calcium concentration leading to

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

. The direct cause of seizures, convulsions, and paralysis are still being investigated.

References

Ichthyotoxins Potassium channel blockers Calcium channel openers Glycoproteins