Tamapin is a toxin from the Indian Red Scorpion (''

Hottentotta tamulus ''Hottentotta tamulus'', the Indian red scorpion, also known as the eastern Indian scorpion, is a species of scorpion of the family Buthidae. It occurs in most of India, eastern Pakistan and the eastern lowlands of Nepal, and recently from Sri ...

''), which is a selective and potent blocker of SK2 channels.

Etymology

Tamapin is named after the

scorpion Scorpions are predatory arachnids of the Order (biology), order Scorpiones. They have eight legs and are easily recognized by a pair of Chela (organ), grasping pincers and a narrow, segmented tail, often carried in a characteristic forward cur ...

from which it was isolated.

Sources

Tamapin has been isolated from ''

hottentotta tamulus ''Hottentotta tamulus'', the Indian red scorpion, also known as the eastern Indian scorpion, is a species of scorpion of the family Buthidae. It occurs in most of India, eastern Pakistan and the eastern lowlands of Nepal, and recently from Sri ...

'', the Indian red scorpion.

Chemical structure and methods of isolation

Tamapin belongs to short-chain scorpion toxin subfamily 5, together with PO5 and

Scyllatoxin Scyllatoxin (also leiurotoxin I) is a toxin, from the scorpion '' Leiurus quinquestriatus hebraeus'', which blocks small-conductance Ca2+-activated K+ channels. It is named after Scylla, a sea monster from Greek mythology. Charybdotoxin is also ...

. Its sequence similarity to other toxins that can compete with the binding site of

apamin Apamin is an 18 amino acid globular 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 syste ...

is much lower. It is 31 amino acids long and its weight is 3458

dalton Dalton may refer to: Science * Dalton (crater), a lunar crater * Dalton (program), chemistry software * Dalton (unit) (Da), a.k.a. unified atomic mass unit * John Dalton, chemist, physicist and meteorologist * 12292 Dalton, an asteroid Ent ...

s. Its amino acid sequence is AFCNLRRCELSCRSLGLLGKCIGEECKCVPY, with disulfide bonds between Cys3-Cys21, Cys8-Cys26, and Cys12-Cys28 (

chemical formula 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 pare ...

C₁₄₆H₂₃₄N₄₂O₄₂S₆). Tamapin has been isolated via detection of the apamin-competing fraction of the venom from the scorpion via a

Sephadex Sephadex is a cross-linked dextran gel used for gel filtration. It was launched by Pharmacia Pharmacia was a pharmaceutical and biotechnological company in Sweden that merged with the American pharmaceutical company Upjohn in 1995. History ...

G-50

size exclusion chromatography Size-exclusion chromatography, also known as molecular sieve chromatography, is a chromatographic method in which molecules in solution are separated by their shape, and in some cases size. It is usually applied to large molecules or macromolecu ...

, followed by

high performance liquid chromatography High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify specific components in mixtures. The mixtures can origina ...

(HPLC). 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 A synaptosome is an isolated synaptic terminal from a neuron. Synaptosomes are obtained by mild homogenization of nervous tissue under isotonic conditions and subsequent fractionation using differential and density gradient centrifugation. Liquid ...

Target and mode of action

The target of tamapin is the small conductance calcium-dependent potassium (SK) channel. This

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

blocks SK2 channels with selectivity for SK2 versus SK1 channels in a largely reversible manner. Despite completely different sequences,

Apamin Apamin is an 18 amino acid globular 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 syste ...

(a bee venom toxin) and tamapin share at least in part, the same binding sites on rat brain

. Cloned SK2 are most sensitive for

in binding assays and physiological recordings. However, tamapin displaces Apamin in binding assays and is therefore a stronger

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. A less closely related member of the

SK channel SK channels (small conductance calcium-activated potassium channels) are a subfamily of calcium-activated potassium channels. They are so called because of their small single channel conductance in the order of 10 pS. SK channels are a type of i ...

s 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. The same applies to voltage dependent potassium channels; the block of SK2-mediated currents is not voltage dependent. This specific channel block evokes a reduction in the small conductance calcium-dependent potassium channels current.

Toxicity

Previous studies showed that the effect of tamapin is largely reversible and depends on time and concentration. The Indian red scorpion (Hottentotta tamulus) causes a large number of deaths annually especially among young children. Its

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...

contains highly specific

potassium channel blockers Potassium channel blockers are agents which interfere with conduction through potassium channels. Medical uses Arrhythmia Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic age ...

such as

iberiotoxin Iberiotoxin (IbTX) is an ion channel toxin purified from the Eastern Indian red scorpion ''Hottentotta tamulus''. Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels. Chemistry Iberiotoxi ...

, which is a highly specific blocker of the high conductance calcium activated potassium channel, and tamulustoxin.

References

{{Reflist, 2 Neurotoxins Ion channel toxins