Kaliseptine

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 (DTX_I) receptor domain on the voltage-gated potassium channel K_V1.2.^[1] The IC₅₀ for inhibition of the K_V1.2 K⁺ channel by kaliseptine is 140 nM as compared to 2.1 nM by DTX_I itself.^[1] The K_V1.2 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 DTX_I does.^[1]

Mode of action

Kaliseptine has been shown to reduce ion current through the K_V1.2 K⁺ channel during depolarization.^[1] Since it has affinity for the DTX_I receptor domain, kaliseptine may act on the channel in a similar manner as the agonist DTX_I. Whether kaliseptine exerts its action by hindering conformational changes of the K_V1.2 channel, is not certain. Evidence was provided that DTX_I 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 K_V1.2 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