User:Negah.filipa/BmKAEP

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BmKAEP
 BmKAEP' (or anti-epilepsy peptide) is a 61 amino acid neurotoxin from the venom of the scorpion Mesobuthus martensii (which historic name is Buthus Martensii'' Karsch) that modifies the gating process of Na+ channels by shifting the activation voltage of sodium channels toward more negative potentials.

Etymology
BmK is the abbreviation for Buthus martensi Karsch, the scorpion that is the source of BmKAEP, whereas AEP corresponds to the anti-epilepsy peptide.

Source
BmKAEP is one of the components of Mesobuthus martensii 's venom, a well-known scorpion belonging to the Buthidae family , which is distributed through Eastern-Asia and China.

Chemistry


BmKAEP is a β-toxin, which inhibits Na+ channels. β-toxins act by modifying voltage-gated Na+ channels' activation process. These toxins are classified according to the target-animal and to the modification they cause. Thus, there are mammal (as mice and rats) and insect β-toxins and these can be excitatory or, as BmKAEP, depressant.

BmKAEP is a 61 amino acid mature protein derived from an 85 amino acid precursor. The mature protein contains 8 cystein residues that establish 4 disulfide bridges (4C-C). Despite its high homology with other depressant toxins, BmKAEP differs from them at residues 6, 7 and 39, which is thought to be important in determining its unique function. Its lysine residue, at position 51, also has a special feature: it interacts with mammalian Na+ channels.

Target and Mode of Action
BmKAEP binds to the site 4 (S4) of voltage-gated Na+ channels, at domains I, III and IV. Its interaction with the S4 loop causes the loop to be maintained at the outward activated position. Therefore, Na+ channel's voltage-dependent activation shifts towards more negative values, enhancing the channel's activation and promoting spontaneous and repetitive firing. Subsequently, the sodium current amplitude decreases, due to the depolarized environment inside the cell, suppressing action potentials.

Toxicity
BmK venom induces a transient phase of contraction followed by a slow progressive flaccid paralysis in insect larvae. However, since it requires a high dosage to be effective, its toxicity is weak, both in insects and mammals.

Therapeutic use
Though the exact mechanism of its anti-epilepsy effect is not clear, several studies have shown that BmKAEP can inhibit coriaria lactone-induced epilepsy in rats by prolonging the latent epilepsy period, relieving the degree of seizures and shortening its average duration, at a pharmacological dosage of only 0,057µg/g. This approach has not been tried in Humans.

Mesobuthus martensii, specially its tail, has been used in Chinese traditional medicine to treat several neuronal diseases, such as several types of paralysis, apoplexy and epilepsy.