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Apamin



Apamin Preproprotein
Protein Structure/Function
Protein length: 46 (precursor) (Amino Acids)
Other
Taxa expressing:Apis mellifera (Western Honeybee)
Cell types:Venom Gland
Database Links
Entrez: 406135
RefSeq: NP_001011612.1
UniProt: P01500
Related information
Related articles:SK channel
Apamin
Identifiers
CAS number 24345-16-2
PubChem 16133797
Properties
Molecular formula C79H131N31O24S4
Molar mass 2027.33874 g/mol
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Apamin is a neurotoxin which selectively blocks SK channels, a type of Ca2+-activated K+ channels expressed in the central nervous system. The final 18 amino acid polypeptide is a component of apitoxin (bee venom).[1] It is used primarily in biomedical research to study the electrical properties of SK channels and their role in the afterhyperpolarizations occurring immediately following an action potential.[2]

Additional recommended knowledge

Contents

Origin

Apamin is a neurotoxin that was originally isolated from Apis mellifera, the Western honey bee. The venom of the honeybee consists of many more products, like melittin, the MCD peptide and phospholipase A2.

Chemistry

Apamin is a polypeptide possessing an amino acid sequence of C00H-Cys-Asn-Cys-Lys-Ala-Pro-Glu-Thr-Ala-Leu-Cys-Ala-Arg-Arg-Cys-Gln-Gln-His-NH2 (with disulfide bonds between Cys1-Cys11 and Cys3-Cys15). Because honeybee venom is a complex mixture of short peptides and proteins, it is difficult to isolate apamin. The isolation can be done by electrophoresis,[3] or by chromatography.[4][5]

Pharmacology

Apamin binds to the SK channels (small conductance Ca2+-activated K+ channels) in the brain and spinal cord and inhibits them.[6] It inhibits the three cloned SK channel subtypes (SK1, SK2, and SK3) with different affinity, highest affinity for SK2, lowest for SK1, and intermediate for SK3 channels. Heteromers show intermediate sensitivity. Most likely, apamin acts as a pore blocker, although residues both inside and outside of the pore region of the SK channels participate in apamin binding.[7] The SK channels are present in a wide range of excitable and non-excitable cells, including cells in the central nervous system, intestinal myocytes, endothelial cells, and hepatocytes. SK channels, when activated, contribute to afterhyperpolarizations in neurons, which control neuronal excitability. Intracellular Ca2+ binding to calmodulin can activate these channels. Channel deactivation can take place through dissociation of Ca2+ from calmodulin.[8] Inhibition of SK channels by apamin will increase the neuronal excitability and lower the threshold for generating an action potential. Other toxins that block SK channels are tamapin and scyllatoxin.

Toxicity

Symptoms following bee sting or apamin poisoning may include:

Patients poisoned with bee venom can be treated with anti-inflammatory medication, antihistamines and oral prednisolone.[9]

Therapeutic Use

SK channel blockers such as apamin can have therapeutic applications, for example on the peripheral cells (e.g. the insulin releasing cells of the pancreas) and on the central nervous system where there is evidence for a role of SK channels in memory processes, both general and specifically hippocampal.[8]

SK channels have been proposed as targets for the treatment of ataxia, epilepsy, memory disorders, and possibly schizophrenia and Parkinson's disease.

References

  1. ^ Habermann E. "Apamin." Pharmacology and Therapeutics. 1984; 25(2):255-70. PMID 6095335
  2. ^ Castle NA, Haylett DG, Jenkinson DH. "Toxins in the characterization of potassium channels." Trends in Neurosciences. 1989 Feb;12(2): 59-65. PMID 2469212
  3. ^ Hartter P, Weber U. "Basic peptides from bee venom, I: isolation, reduction and reoxidation of apamin and MCD-peptide." Hoppe Seylers Z Physiol Chem. 1975 Jun; 356(6):693-9. PMID 1181269
  4. ^ Räder K, Wildfeuer A, Wintersberger F, Bossinger P, Mücke HW. "Characterization of bee venom and its main components by high-performance liquid chromatography." Journal of Chromatography. 1987 Nov 6;408:341-8. PMID 3429530
  5. ^ Loseva OI, Gavryushkin AV, Osipov VV, Vanyakin EN. "Application of free-flow electrophoresis for isolation and purification of proteins and peptides." Electrophoresis. 1998 Jun;19(7):1127-34. PMID 9662174
  6. ^ Fletcher DI, Ganellin CR, Piergentili A, Dunn PM, Jenkinson DH. "Synthesis and pharmacological testing of polyaminoquinolines as blockers of the apamin-sensitive Ca2+-activated K+ channel (SK(Ca))." Bioorganic Medical Chemistry. 2007 Aug 15;15(16):5457-79. PMID 17560109
  7. ^ Nolting, A., Ferraro, T. D'hoedt, D. and Stocker, M. "An Amino Acid Outside the Pore Region Influences Apamin Sensitivity in Small Conductance Ca2+-activated K+ Channels." Journal of Biological Chemistry. 2007 282, 3478-3486. PMID 17142458
  8. ^ a b Stocker M. "Ca(2+)-activated K+ channels: molecular determinants and function of the SK family." Nature Reviews Neuroscience. 2004 Oct;5(10):758-70. PMID 15378036
  9. ^ a b R. Saravanan R, King J, White J. "Transient claw hand owing to a bee sting. A report of two cases." The Journal of Bone and Joint Surgery (Br). 2004;86-B;404-5. PMID 15125129
  10. ^ Lallement G, Fosbraey P, Baille-Le-Crom V, Tattersall JE, Blanchet G, Wetherell JR, Rice P, Passingham SL, Sentenac-Roumanou H. "Compared toxicity of the potassium channel blockers, apamin and dendrotoxin." Toxicology. 1995 Dec 15;104(1-3):47-52. PMID 8560501
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Apamin". A list of authors is available in Wikipedia.
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