BmKAEP (or anti-epilepsy peptide) is aneurotoxin from thevenom of theManchurian scorpion(Mesobuthus martensii). It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.
BmK is the abbreviation forButhus martensi Karsch, an old name for the scorpion that is the source of BmKAEP; AEP is an abbreviation for anti-epilepsy peptide. At theNCBI Protein Database, the full name of this peptide is listed as "Toxin BmKAEP".[1]
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BmKAEP is one of the components ofMesobuthus martensii's venom,[2] a well-known scorpion belonging to the familyButhidae, which is found distributed throughout Eastern Asia and China.
BmKAEP is an inhibitoryβ-toxin and thus, a Na+ channel inhibitor. As with other mammal and insect toxins, BmKAEP is classified according to species and mechanism of action.[3]
BmKAEP is a 61-amino-acid protein derived from an 85-amino-acid precursor. The mature protein contains 8 cysteine residues that establish 4disulfide bridges (4C-C).[3] 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.[3] Its lysine residue, at position 51, also has a special feature: it interacts with mammalian Na+ channels.[4]
| BmKAEP primary sequence[5] |
|---|
01 mklflllvis asmlidglvn adgyirgsng |
Because of its sequence homology with other β-toxins, BmKAEP is predicted to bind to site 4 (S4) ofvoltage-gated Na+ channels, at domains I, III and IV.[6] Its interaction with the S4 loop causes the loop to be maintained at the outward activated position. Therefore, activation of the Na+ channels shifts towards more negative values,[7] enhancing the channel's activation and promoting spontaneous and repetitive firing. Subsequently, the sodium current amplitude decreases, due to the membrane potential depolarization, thus suppressingaction potentials.[2]
BmK venom induces a transient phase of contraction followed by a slow progressiveflaccid paralysis in insect larvae.[8] However, since it requires a high dosage to be effective, its toxicity is weak, both in insects and mammals.[9]
| Toxicity parameters | |
|---|---|
| LD50 | 2,4 mg/kg(mice; intraperitoneal injection)[3] |
| MLD(minimum lethal dose) | 0,074 mg/kg(mice; Intracerebroventricular injection)[2] |
| CPU(concentration paralysis unit) | 1 μg/body(larvae)[2] |
| NOAEL(No observed adverse effect) | <2 μg(insects); <20 μg(mice)[3] |
Though the exact mechanism of its anti-epilepsy effect is not clear, several studies have shown that BmKAEP can inhibitcoriarialactone-inducedepilepsy in rats by prolonging the latent epilepsy period, relieving the degree ofseizures and shortening its average duration, at a pharmacological dosage of only 0.057 μg/g.[9]
Mesobuthus martensii, especially its tail, has been used inChinese traditional medicine to treat several neuronal diseases, such as several types ofparalysis,apoplexy and epilepsy.[2]
