{{Short description|Lethal venom produced by Synanceia verrucosa}} '''Verrucotoxin''' ('''VTX''') is a lethal venom produced by the dorsal fins of ''Synanceia verrucosa''. This species of reef stonefish is connected to the family ''Synanceiidae''. The venom of this species of stonefish is a tetrameric glycoprotein with cardiovascular and cytolytic effects.<ref name=":0" />
== 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).<ref name=":0" /> Verrucotoxin shares a total of 96% homology to the closely related venom stonustoxin beta subunit.<ref name=":0">{{Cite journal|last1=Yazawa|first1=K|last2=Wang|first2=J-W|last3=Hao|first3=L-Y|last4=Onoue|first4=Y|last5=Kameyama|first5=M|date=August 2007|title=Verrucotoxin, a stonefish venom, modulates calcium channel activity in guinea-pig ventricular myocytes|journal=British Journal of Pharmacology|volume=151|issue=8|pages=1198–1203|doi=10.1038/sj.bjp.0707340|issn=0007-1188|pmc=2189832|pmid=17572694}}</ref> Stonustoxin is the venom produced from ''Synanceia horrida''.
== Function and mechanism == Verrucotoxin has been studied to interact with both calcium ion channels and potassium ATP channels.<ref name=":0" /><ref name=":1">{{Cite journal|last1=Wang|first1=Jian-Wu|last2=Yazawa|first2=Kazuto|last3=Hao|first3=Li-Ying|last4=Onoue|first4=Yoshio|last5=Kameyama|first5=Masaki|date=June 2007|title=Verrucotoxin inhibits KATP channels in cardiac myocytes through a muscarinic M3 receptor-PKC pathway|url=https://linkinghub.elsevier.com/retrieve/pii/S001429990700177X|journal=European Journal of Pharmacology|language=en|volume=563|issue=1–3|pages=172–179|doi=10.1016/j.ejphar.2007.02.004|pmid=17362922|url-access=subscription}}</ref> The calcium ion channel is modulated by the activation of the β-adrenoceptors when verrucotoxin binds. There are three subunits of β-adrenoceptors, β1, β2, and β3, but only β2-adrenoceptors are responsible for the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase (PKA) pathway.<ref name=":0" /><ref name=":2">{{Cite journal|last=Johnson|first=Malcolm|date=1998-11-01|title=The β -Adrenoceptor|url=https://www.atsjournals.org/doi/10.1164/ajrccm.158.supplement_2.13tac110|journal=American Journal of Respiratory and Critical Care Medicine|volume=158|issue=supplement_2|pages=S146–S153|doi=10.1164/ajrccm.158.supplement_2.13tac110|pmid=9817738|issn=1073-449X|url-access=subscription}}</ref> The cAMP will phosphorylate muscle regulatory proteins and modulate intercellular calcium concentrations.<ref name=":2" /> 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.<ref name=":0" /> 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.<ref name=":0" />
The second method verrucotoxin disrupts cells are through potassium ion channels, particularly the potassium adenosine triphosphate (KATP) pathway.<ref name=":1" /> The potassium ATP channel operates by pumping potassium ions out of the intercellular membrane.<ref name=":3">{{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}}</ref> It’s capable of doing so by phosphorylating the channel with adenosine triphosphate (ATP).<ref name=":3" /> Verrucotoxin is able to inhibit the operation of the potassium ATP through the activation of muscarinic M3 receptor-protein kinase C (PKC).<ref name=":1" /> It is the activation of the PKC that will inhibit the potassium ion channel.<ref name=":1" /> The PKC is presumably phosphorylating the KATP channel instead of ATP.<ref name=":1" />
== Adverse effects == The stonefish, ''Synanceia verrucosa'', 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, convulsions, respiratory arrest, and damage to the cardiovascular system.<ref name=":0" /> Verrucotoxin has been studied to be the cause of cardiovascular system damage, convulsions, seizures, and paralysis.<ref name=":0" /> For the cardiovascular system damage, it is caused by the sudden change in the intercellular calcium concentration leading to arrhythmia.<ref name=":0" /> The direct cause of seizures, convulsions, and paralysis are still being investigated.<ref name=":0" />
== References == <references />
Category:Ichthyotoxins Category:Potassium channel blockers Category:Calcium channel openers Category:Glycoproteins