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Kaliseptine

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Kaliseptine (AsKS) is a neurotoxin which can be found in the snakelocks anemone Anemonia viridis. It belongs to a class of sea anemone neurotoxins that inhibits voltage-gated potassium channels.

Etymology

“Kali” is derived from the Latin word [kalium], which means potassium. The suffix “septine” is derived from the Greek word “sepsis” [σῆψις], which means “decay” or “putrefaction”. This suffix was added to distinguish it from the related toxin kalicludine.[1] Kaliseptine was first isolated from the snakelocks anemone, which at the time was called Anemonia sulcata. Kaliseptine is abbreviated as AsKS, which stands for Anemonia sulcata KaliSeptine.[1]
The rational nomenclature of kaliseptine is kappa-actitoxin-Avd6a.[2] The first letter Kappa indicates its molecular target, namely a voltage-gated potassium channel. Actitoxin is a neurotoxin derived from the Actiniidae. Avd denotes that it is extracted from Anemonia viridis. Finally, 6a specifies that this was the sixth Acititoxin of which the full-length amino acid sequence was published and that this is the first isoform.[2][3]

Sources

Kaliseptine was first isolated from the snakelocks anemone Anemonia viridis, previously known as Anemonia sulcata.[1] The snakelocks anemone releases its venom via both nematocysts and ectodermal glands. Kaliseptine is a type I anemone toxin.[4] Although typically the type I toxins are located in both organelles, the location for kaliseptine has not yet been reported.[5]

Biochemistry

Kaliseptine is a 36 amino acid peptide and contains three disulfide bonds.[1][4] Kaliseptine shows structural similarities with other sea anemone toxins like Actinia equina K+-channel toxin (AeK), Bunodosoma granulifera K+-channel toxin (BgK) and Stichodactyla helianthus K+-channel toxin (ShK). These toxins can be classified as type I voltage-gated potassium channel inhibiting peptides, based on their size and structure. Type I peptide toxins typically consist of 35 to 37 amino acids and show a high rate of homology in amino acid sequence.[4][6]
The residues which are demonstrated to be most essential for potassium channel binding are the adjacent Lys-24 and Tyr-25, which are conserved in all four orthologous peptides. The allosteric effects of this binding have not been reported.[4][7]

Target

Kaliseptine competitively binds the dendrotoxin (DTXI) receptor domain on the voltage-gated potassium channel KV1.2.[1] The IC50 for inhibition of the KV1.2 K+ channel by kaliseptine is 140 nM as compared to 2.1 nM by DTXI itself.[1] The KV1.2 channel is important for reducing action potential frequency and facilitating repolarisation following an action potential. It is not known whether kaliseptine has any additional targets, like DTXI does.[1]

Mode of action

Kaliseptine has been shown to reduce ion current through the KV1.2 K+ channel during depolarization.[1] Since it has affinity for the DTXI receptor domain, kaliseptine may act on the channel in a similar manner as the agonist DTXI. Whether kaliseptine exerts its action by hindering conformational changes of the KV1.2 channel, is not certain. Evidence was provided that DTXI binds in close proximity to the external mouth of the channel, leading to occlusion of the pore.[8] It is not certain whether this partial occlusion fully explains the inhibiting effect.[9] The exact mechanism by which Kaliseptine alters KV1.2 function is still debated. Kaliseptine is thought to act in conjunction with other neurotoxins present in the snakelocks anemone venom, altogether prolonging the action potential.[10]

Toxicity

Limited in vitro studies were performed on the toxic effects of isolated kaliseptine.[1] The combined venom of the snakelocks anemone is known to be toxic when applied directly onto mammalian hearts.[11][12][13] The venom then causes an increase of the action potential duration.[13] When the nematocysts of the snakelocks anemone come into contact with human skin, the venom can cause redness, swelling and pain.[14]

Treatment

There is no known treatment for intoxication with kaliseptine. The suggested treatment for the venom of snakelocks anemone consists of symptomatic treatment and prevention of further nematocyst discharge.[15][16]

References

  1. ^ a b c d e f g h i Schweitz, H.; Bruhn, T. (20 October 1995). "Kalicludines and kaliseptine. Two different classes of sea anemone toxins for voltage sensitive K+ channels". The Journal of Biological Chemistry. 270 (42): 25121–25126. doi:10.1074/jbc.270.42.25121. PMID 7559645.
  2. ^ a b Oliveira, J.S.; Fuentes-Silva, D. (15 September 2012). "Development of a rational nomenclature for naming peptide and protein toxins from sea anemones". Toxicon. 60 (4): 539–550. doi:10.1016/j.toxicon.2012.05.020. PMID 22683676.
  3. ^ "UniProtKB - Q9TWG1 (TXT1B_ANESU)". UniProt. Retrieved 7 October 2015.
  4. ^ a b c d Minagawa, S.; Ishida, M. (1 May 1998). "Primary structure of a potassium channel toxin from the sea anemone Actinia equina". FEBS Letters. 427 (1): 149–151. doi:10.1016/s0014-5793(98)00403-7. PMID 9613617.
  5. ^ Moran, Y.; Genikhovich, G. (7 April 2012). "Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones". Proceedings of the Royal Society B. 279 (1732): 1351–1358. doi:10.1098/rspb.2011.1731. PMC 3282367. PMID 22048953.
  6. ^ Honma, T.; Shiomi, K. (January 2006). "Peptide toxins in sea anemones: structural and functional aspects". Marine Biotechnology. 8 (1): 1–10. doi:10.1007/s10126-005-5093-2. PMC 4271777. PMID 16372161.
  7. ^ Pennington, M.W.; Mahnir, V.M. (1996). "An essential binding surface for ShK toxin interaction with rat brain potassium channels". Biochemistry. 35 (51): 16407–16411. doi:10.1021/bi962463g. PMID 8987971.
  8. ^ Hurst, R.S.; Busch, A.E. (October 1991). "Identification of amino acid residues involved in dendrotoxin block of rat voltage-dependent potassium channels". Molecular Pharmacology. 40 (4): 572–576. PMID 1921987.
  9. ^ Imredy, J.P.; MacKinnon, R. (March 2000). "Energetic and structural interactions between delta-dendrotoxin and a voltage-gated potassium channel". Journal of Molecular Biology. 296 (5): 1283–1294. doi:10.1006/jmbi.2000.3522. PMID 10698633.
  10. ^ Isenberg, G.; Ravens, U. (December 1984). "The effects of the Anemonia sulcata toxin (ATX II) on membrane currents of isolated mammalian myocytes". The Journal of Physiology. 357: 127–149. doi:10.1113/jphysiol.1984.sp015493. PMC 1193251. PMID 6150992.
  11. ^ Alsen, C.; Béress, L. (October 1976). "The action of a toxin from the sea anemone Anemonia sulcata upon Mammalian heart muscles". Naunyn-Schmiedeberg's Archives of Pharmacology. 295 (1): 55–62. doi:10.1007/bf00509773. PMID 12483.
  12. ^ Tazieff-Depierre, F.; Choucavy, M. (27 September 1976). "Pharmacologic properties of the toxins isolated from the sea anemone (Anemonia sulcata)". Comptes Rendus de l'Académie des Sciences, Série D. 283 (6): 699–702. PMID 186216.
  13. ^ a b Hoey, A.; Harrison, S.M. (December 1994). "Effects of the Anemonia sulcata toxin (ATX II) on intracellular sodium and contractility in rat and guinea-pig myocardium". Parmacology & Toxicology. 75 (6): 356–365. doi:10.1111/j.1600-0773.1994.tb00375.x. PMID 7899257.
  14. ^ Maretić, Z.; Russell, F.E. (July 1983). "Stings by the sea anemone Anemonia sulcata in the Adriatic Sea". The American Journal of Tropical Medicine and Hygiene. 32 (4): 891–896. PMID 6136192.
  15. ^ Abody, Z.; Klein-Kremer, A. (October 2006). "Anemonia sulcata sting". Harefuah. 145 (10): 736–737. PMID 17111708.
  16. ^ Rosson, C.L.; Tolle, S.W. (January 1989). "Management of marine stings and scrapes". The Western Journal of Medicine. 150 (1): 97–100. PMC 1026320. PMID 2567557.
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