BmKAEP (or anti-epilepsy peptide) is a

neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpencer 2000 that can adversely affect function ...

from the

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 ...

of the Manchurian scorpion ''(Mesobuthus martensii)''. It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.

Etymology

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 The National Center for Biotechnology Information (NCBI) is part of the National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The NCBI is loca ...

Protein Database, the full name of this peptide is listed as "Toxin BmKAEP".

Sources

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

Chemistry

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. 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). 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

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. 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, 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 potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

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 Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

in rats by prolonging the latent epilepsy period, relieving the degree of

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

and shortening its average duration, at a pharmacological dosage of only 0.057 μg/g. ''Mesobuthus martensii'', especially its tail, has been used in Chinese traditional medicine to treat several neuronal diseases, such as several types of

paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...

apoplexy Apoplexy () refers to the rupture of an internal organ and the associated symptoms. Informally or metaphorically, the term ''apoplexy'' is associated with being furious, especially as "apoplectic". Historically, it described what is now known as a ...

and epilepsy.

References

External links

* NCBI Protein Database for "Toxin BmKAEP"
AEP1_MESMA, ACCESSION: P15228.2, GI:37999913
{{DEFAULTSORT:Bmkaep Neurotoxins Ion channel toxins Scorpion toxins