Iberiotoxin
Encyclopedia
The amino acid sequence of Iberiotoxin
Pyr - Phe - Thr - Asp - Val - Asp - Cys - Ser - Val - Ser - Lys - Glu - Cys - Trp - Ser - Val - Cys - Lys - Asp - Leu - Phe - Gly - Val - Asp - Arg - Gly - Lys - Cys - Met - Gly - Lys - Lys - Cys - Arg - Cys - Tyr - Gln - OH
Disulfide bridges: Cys7 - Cys28, Cys13 - Cys33, Cys17 - Cys35


Iberiotoxin is an ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

 toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 purified from the Eastern Indian red scorpion
Scorpion
Scorpions are predatory arthropod animals of the order Scorpiones within the class Arachnida. They have eight legs and are easily recognized by the pair of grasping claws and the narrow, segmented tail, often carried in a characteristic forward curve over the back, ending with a venomous stinger...

 Buthus tamulus.
Iberiotoxin selectively inhibits the current
Electric current
Electric current is a flow of electric charge through a medium.This charge is typically carried by moving electrons in a conductor such as wire...

 through large-conductance calcium-activated potassium channel
Calcium-activated potassium channel
Calcium-activated potassium channels are divided into BK channels, IK channels, and SK channels based on their conductance ....

s.

Chemistry

Iberiotoxin is a 37-amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

. It is also known as "Potassium channel toxin alpha-KTx 1.3" or IbTx. The complete amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 sequence has been defined and it displays 68% sequence homology with charybdotoxin
Charybdotoxin
Charybdotoxin is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system.-Chemical properties:...

.

Target and mode of action

Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels (maxiK or BK channel
BK channel
BK channels , also called Maxi-K or slo1, are ion channels characterized by their large conductance of potassium ions through cell membranes. These channels are activated by changes in membrane electrical potential and/or by increases in concentration of intracellular calcium ion...

s) with high affinity (Kd ~1 nM). It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.

Toxicity

The venom produces mainly cardiopulmonary abnormalities like circulatory derangements, myocarditis
Myocarditis
Myocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...

 and changes in cardiac sarcolemma
Sarcolemma
The sarcolemma is the cell membrane of a muscle cell . It consists of a true cell membrane, called the plasma membrane, and an outer coat made up of a thin layer of polysaccharide material that contains numerous thin collagen fibrils...

l ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...

 and by these abnormalities it can finally cause death. In rural India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

 the scorpion and its venom is a commonly known factor of children's death. The venom initially causes transient cholinergic
Cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

 stimulation (vomiting, profuse sweating
Sweating
Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...

, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

, priapism
Priapism
Priapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow...

, hypersalivation
Hypersalivation
Hypersalivation is excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva....

, and hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

) which is followed by sustained adrenergic
Adrenergic
An adrenergic agent is a drug, or other substance, which has effects similar to, or the same as, epinephrine . Thus, it is a kind of sympathomimetic agent...

 hyperactivity (hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, and myocardial failure). The adrenergic phase but not the cholinergic phase is a dose-dependent phenomenon.

Treatment

Treatment is mainly symptomatic. Local pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

 is treated by injecting dehydroemetine
Dehydroemetine
Dehydroemetine is a synthetically produced antiprotozoal agent similar to emetine in its anti-amoebic properties and structure , but it produces fewer side effects...

 at the site of the sting. Hypovolaemia is corrected by oral rehydration solution. Agitated, confused and non-cooperative patients are given a 5% dextrose saline
Saline (medicine)
In medicine, saline is a general term referring to a sterile solution of sodium chloride in water but is only sterile when it is to be placed intravenously, otherwise, a saline solution is a salt water solution...

 drip. Patients with hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

 on admission are given a single dose of 5 mg sublingual
Sublingual
Sublingual, literally 'under the tongue', from Latin, refers to the pharmacological route of administration by which drugs diffuse into the blood through tissues under the tongue...

 nifedipine
Nifedipine
Nifedipine is a dihydropyridine calcium channel blocker...

 and oral prazosin
Prazosin
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...

. The blood pressure in patients with hypertension is controlled with sublingual nifedipine alone. Patients with pulmonary oedema are propped up and given intravenous aminophylline
Aminophylline
Aminophylline is a bronchodilator. It is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate-Properties:...

, intravenous sodium bicarbonate
Intravenous sodium bicarbonate
Intravenous sodium bicarbonate is a solution for intravenous administration that increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis....

, oral prazosin
Prazosin
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...

, and oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

by mask.
The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK