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.

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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]

Related Research Articles

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Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes (Dendroaspis) that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions. Because of their high potency and selectivity for potassium channels, dendrotoxins have proven to be extremely useful as pharmacological tools for studying the structure and function of these ion channel proteins.

<i>Anemonia sulcata</i> Species of sea anemone

Anemonia sulcata, or Mediterranean snakelocks sea anemone, is a species of sea anemone in the family Actiniidae from the Mediterranean Sea. Whether A. sulcata should be recognized as a synonym of A. viridis remains a matter of dispute.

<span class="mw-page-title-main">Sea anemone neurotoxin</span>

Sea anemone neurotoxin is the name given to neurotoxins produced by sea anemones with related structure and function. Sea anemone neurotoxins can be divided in two functional groups that either specifically target the sodium channel or the potassium channel.

Mast cell degranulating (MCD) peptide is a cationic 22-amino acid residue peptide, which is a component of the venom of the bumblebee. At low concentrations, MCD peptide can stimulate mast cell degranulation. At higher concentrations, it has anti-inflammatory properties. In addition, it is a potent blocker of voltage-sensitive potassium channels.

AETX refers to a group of polypeptide neurotoxins isolated from the sea anemone Anemonia erythraea that target ion channels, altering their function. Four subtypes have been identified: AETX I, II, III and K, which vary in their structure and target.

Hemitoxin (HTX; α-KTx6.15) is a 35-mer basic peptide from the venom of the Iranian scorpion Hemiscorpius lepturus, which reversibly blocks Kv1.1, Kv1.2 and Kv1.3voltage-gated K+ channels.

Parabutoxin (PBTx) is a Shaker-related voltage-gated K+ channel (Kvα1) inhibitor purified from different Parabuthus scorpion species found in southern Africa. It occurs in different forms: parabutoxin 1 (PBTx1), parabutoxin 2 (PBTx2), parabutoxin 3 (PBTx3) and parabutoxin (PBTx10). The different variants have different affinities towards Kvα1 channels.

Anuroctoxin is a peptide from the venom of the Mexican scorpion Anuroctonus phaiodactylus. This neurotoxin belongs to the alpha family of potassium channel acting peptides. It is a high-affinity blocker of Kv1.3 channels.

<span class="mw-page-title-main">Pandinus imperator (Pi3) toxin</span>

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Calitoxin, also known as CLX, is a sea anemone neurotoxin produced by the sea anemone Calliactis parasitica. It targets crabs and octopuses, among other invertebrates. Two isoforms have been identified, both of which are formed from precursors stored in the stinging cells of the anemone. Once the toxin is activated and released, it causes paralysis by increasing neurotransmitter release at invertebrate neuromuscular junctions. Along with several other toxins derived from anemones, CLX is useful in ion channel research. Certain structural aspects of calitoxin are dissimilar from sea anemone toxins that also target the sodium ion channels. Other toxins resembling calitoxin function in completely different ways.

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Blood-depressing substance-1 (BDS-1), also known as kappa-actitoxin-Avd4a, is a polypeptide found in the venom of the snakelocks anemone Anemonia sulcata. BDS-1 is a neurotoxin that modulates voltage-dependent potassium channels, in particular Kv3-family channels, as well as certain sodium channels. This polypeptide belongs to the sea anemone type 3 toxin peptide family.

HsTx1 is a toxin from the venom of the scorpion Heterometrus spinifer. HsTx1 is a very potent inhibitor of the rat Kv1.3 voltage-gated potassium channel.

Spinoxin is a 34-residue peptide neurotoxin isolated from the venom of the Malaysian black scorpion Heterometrus spinifer. It is part of the α-KTx6 subfamily and exerts its effects by inhibiting voltage-gated potassium channels, specifically Kv1.2 and Kv1.3.

SHTX is a toxin derived from the sea anemone Stichodactyla haddoni; there are four different subtypes, SHTX I, II, III and IV. SHTX I, II and III can paralyze crabs by acting on potassium channels, while SHTX IV works on sodium channels, and is lethal to crabs.

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ATX-II, also known as neurotoxin 2, Av2, Anemonia viridis toxin 2 or δ-AITX-Avd1c, is a neurotoxin derived from the venom of the sea anemone Anemonia sulcata. ATX-II slows down the inactivation of different voltage-gated sodium channels, including Nav1.1 and Nav1.2, thus prolonging action potentials.

<span class="mw-page-title-main">BscTx3</span>

BcsTx3, also known as Kappa-actitoxin-Bsc4a, is a neurotoxin that blocks voltage-gated potassium channel (Kv1/KCNA). It is purified from the venom of Bunodosoma caissarum.

AsKC11 is a toxin found in the venom of the sea anemone, Anemonia sulcata. This toxin is part of the Kunitz peptide family and has been shown to be an activator of G protein-coupled inwardly-rectifying potassium (GIRK) channels 1/2, involved in the regulation of cellular excitability. 

Kunitz-type serine protease inhibitor APEKTx1 is a peptide toxin derived from the sea anemone Anthopleura elegantissima. This toxin has a dual function, acting both as a serine protease inhibitor and as a selective and potent pore blocker of Kv1.1, a shaker related voltage-gated potassium channel.

References

  1. 1 2 3 4 5 6 7 8 9 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. 1 2 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. Bibcode:2012Txcn...60..539O. doi:10.1016/j.toxicon.2012.05.020. PMID   22683676.
  3. ↑ "UniProtKB - Q9TWG1 (TXT1B_ANESU)". UniProt. Retrieved 7 October 2015.
  4. 1 2 3 4 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. Bibcode:1998FEBSL.427..149M. 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. Bibcode:2006MarBt...8....1H. 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. S2CID   6807646.
  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. 1 2 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. doi:10.4269/ajtmh.1983.32.891. 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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