Tamapin is a toxin from the Indian Red Scorpion ( Mesobuthus tamalus ), which is a selective and potent blocker of SK2 channels.
Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2, also known as KCNN2, is a protein which in humans is encoded by the KCNN2 gene. KCNN2 is an ion channel protein also known as KCa2.2.
Tamapin is named after the scorpion from which it was isolated. [1]
Scorpions are predatory arachnids of the order Scorpiones. They have eight legs and are easily recognized by the pair of grasping pedipalps and the narrow, segmented tail, often carried in a characteristic forward curve over the back, ending with a venomous stinger. Scorpions range in size from 9 mm / 0.3 in. to 23 cm / 9 in..
Tamapin has been isolated from Mesobuthus tamalus , the Indian red scorpion. [2]
Tamapin belongs to short-chain scorpion toxin subfamily 5, together with PO5 and Scyllatoxin. Its sequence similarity to other toxins that can compete with the binding site of apamin is much lower. It is 31 amino acids long and its weight is 3458 Daltons. Its amino acid sequence is given in Table 1. Its amino-acid sequence is "AFCNLRRCELSCRSLGLLGKCIGEECKCVPY" (Chemical formula C146H234N42O42S6). [1]
Scyllatoxin (also leiurotoxin I) is a toxin, from the scorpion Leiurus quinquestriatus hebraeus, which blocks small-conductance Ca2+-activated K+ channels.
Apamin is an 18 amino acid peptide neurotoxin found in apitoxin (bee venom). Dry bee venom consists of 2–3% of apamin. Apamin selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system. Toxicity is caused by only a few amino acids, these are cysteine1, lysine4, arginine13, arginine14 and histidine18. These amino acids are involved in the binding of apamin to the Ca2+-activated K+ channel. Due to its specificity for SK channels, apamin is used as a drug in biomedical research to study the electrical properties of SK channels and their role in the afterhyperpolarizations occurring immediately following an action potential.
A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as parentheses, dashes, brackets, commas and plus (+) and minus (−) signs. These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a chemical name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, and are generally more limited in power than are chemical names and structural formulas.
Tamapin has been isolated via detection of the apamin-competing fraction of the venom from the scorpion via a Sephadex G-50 size exclusion chromatography, followed by high performance liquid chromatography (HPLC). [1] An isoform of tamapin, tamapin-2, has been found, in which the tyrosine is replaced by a histadine. Tamapin-2 can also compete very effectively with apamin for binding to synaptosomes. [1]
Sephadex is a trademark for cross-linked dextran gel used for gel filtration. It was launched by Pharmacia in 1959, after development work by Jerker Porath and Per Flodin. The name is derived from separation Pharmacia dextran. It is normally manufactured in a bead form and most commonly used for gel filtration columns. By varying the degree of cross-linking, the fractionation properties of the gel can be altered.
The target of Tamapin is the small conductance calcium-dependent potassium (SK) channel. This scorpion toxin blocks SK2 channels with selectivity for SK2 versus SK1 channels in a largely reversible manner. [1] Despite completely different sequences, Apamin (a bee venom toxin) and Tamapin share at least in part, the same binding sites on rat brain synaptosomes. Cloned SK2 are most sensitive for Apamin in binding assays and physiological recordings. [1] However, Tamapin displaces Apamin in binding assays and is therefore a stronger toxin with respect to Apamin. SK 1 and SK 3 are only affected with a high concentration of Tapamin and therefore this toxin inhibits SK2 with the highest affinity, SK3 intermediate and the lowest affinity for SK1 channels. [1] A less closely related member of the SK channels is the intermediate conductance calcium activated potassium channel SK4, also known as IK1, which is not sensitive to Apamin and is also not affected by Tapamin. [1] The same applies to voltage dependent potassium channels; the block of SK2-mediated currents is not voltage dependent. [1] This specific channel block evokes a reduction in the small conductance calcium-dependent potassium channels current.
A toxin is a poisonous substance produced within living cells or organisms; synthetic toxicants created by artificial processes are thus excluded. The term was first used by organic chemist Ludwig Brieger (1849–1919).
SK channels (small conductance calcium-activated potassium channels) are a subfamily of Ca2+-activated K+ channels. They are so called because of their small single channel conductance in the order of 10 pS. SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium through N-type calcium channels. Their activation limits the firing frequency of action potentials and is important for regulating afterhyperpolarization in the neurons of the central nervous system as well as many other types of electrically excitable cells. This is accomplished through the hyperpolarizing leak of positively charged potassium ions along their concentration gradient into the extracellular space. This hyperpolarization causes the membrane potential to become more negative. SK channels are thought to be involved in synaptic plasticity and therefore play important roles in learning and memory.
Previous studies showed that the effect of tamapin is largely reversible and depends on time and concentration. The Indian red scorpion (Mesobuthus tamulus) causes a large number of deaths annually especially among young children. [3] Its venom contains highly specific potassium channel blockers such as iberiotoxin, which is a highly specific blocker of the high conductance calcium activated potassium channel, and tamulustoxin. [4]
Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker) that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus.
Omega-grammotoxin SIA is a protein toxin that inhibits P, Q and N voltage-gated calcium channels (Ca2+ channels) in neurons.
Taicatoxin (TCX) is a snake toxin that blocks voltage-dependent L-type calcium channels and small conductance Ca2+-activated K+ channels. The name taicatoxin (TAIpan + CAlcium + TOXIN) is derived from its natural source, the taipan snake, the site of its action, calcium channels, and from its function as a toxin. Taicatoxin was isolated from the venom of Australian taipan snake, Oxyuranus scutellatus scutellatus. TCX is a secreted protein, produced in the venom gland of the snake.
Tityustoxin is a toxin found in the venom of scorpions from the subfamily of Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.
Slotoxin is a peptide from Centruroides noxius Hoffmann scorpion venom. It belongs to the short scorpion toxin superfamily.
Maurotoxin is a peptide toxin from the venom of the Tunisian chactoid scorpion Scorpio maurus palmatus, from which it was first isolated and from which the chemical gets its name. It acts by blocking several types of voltage-gated potassium channel.
Iberiotoxin (IbTX) is an ion channel toxin purified from the Eastern Indian red scorpion Buthus tamulus. Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels.
Phoneutria nigriventer toxin-3 is more commonly referred to as PhTx3.
In molecular biology, the BmKK2 toxins are a family of scorpion toxins. They belong to the scorpion toxin subfamily alpha-KTx 14. They include a novel short-chain peptide from the Asian scorpion Mesobuthus martensii Karsch, a potassium channel blocker composed of 31 amino acid residues. The peptide adopts a classical alpha/beta-scaffold for alpha-KTxs. BmKK2 selectively inhibits the delayed rectifier K+ current, but does not affect the fast transient K+ current.
BeKm-1 is a toxin from the Central Asian scorpion Buthus eupeus. BeKm-1 acts by selectively inhibiting the human Ether-à-go-go Related Gene (hERG) channels, which are voltage gated potassium ion channels.
Pi3 toxin is a purified peptide derivative of the Pandinus imperator scorpion venom. It is a potent blocker of voltage-gated potassium channel, Kv1.3 and is closely related to another peptide found in the venom, Pi2.
Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.
HsTx1 is a toxin from the venom of the scorpion Heterometrus spinifer. HsTx1 is a very potent inhibitor of the rat Kv1.3 voltage-gated potassium channel.
Pi4 is a short toxin from the scorpion Pandinus imperator that blocks specific potassium channels.
Limbatustoxin, is an ion channel toxin from the venom of the Centruroides limbatus scorpion. This toxin is a selective blocker of BK channels, calcium-activated potassium channels.
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.
BmP02, also known as α-KTx 9.1 or Bmkk(6), is a toxin from the Buthus Martensi Karsch (BmK) scorpion. The toxin acts on potassium channels, blocking Kv1.3 and slowing the deactivation of Kv4.2. BmP02 is not toxic to humans or mice.