BmKAEP

BmK is the abbreviation for Buthus martensi Karsch, an old name for the scorpion that is the source of BmKAEP; AEP is an abbreviation for anti-epilepsy peptide. At the NCBI Protein Database, the full name of this peptide is listed as "Toxin BmKAEP".^[1]

BmKAEP is one of the components of Mesobuthus martensii's venom,^[2] a well-known scorpion belonging to the family Buthidae, which is found distributed throughout Eastern Asia and China.

BmKAEP is an inhibitory β-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 4 disulfide 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]

Because of its sequence homology with other β-toxins, BmKAEP is predicted to bind to site 4 (S4) of voltage-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 suppressing action potentials.^[2]

BmK venom induces a transient phase of contraction followed by a slow progressive flaccid 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]

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 0.057 μg/g.^[9]

Mesobuthus martensii, especially its tail, has been used in Chinese traditional medicine to treat several neuronal diseases, such as several types of paralysis, apoplexy and epilepsy.^[2]