Taicatoxin
Taicatoxin (TCX) is a snake toxin that blocks voltage-dependent L-type calcium channels and small conductance Ca2+-activated K+ channels. The name taicatoxin (TAIpan + CAlcium + TOXIN) is derived from its natural source, the taipan snake, the site of its action, calcium channels, and from its function as a toxin. Taicatoxin was isolated from the venom of Australian taipan snake, Oxyuranus scutellatus scutellatus. TCX is a secreted protein, produced in the venom gland of the snake.[1]
Chemistry
Through
- a α-neurotoxin-like peptide (8 kDa),
- a neurotoxic phospholipase (16 kDa;[3]) and
- a serine protease inhibitor (7 kDa;[4]).
The active complex was isolated by ion exchange chromatography through DE-Cellulose and two steps of Cm-Cellulose chromatography at pH = 4.7 and pH = 6.0, respectively. It migrates in beta-alanine-acetate-urea gel electrophoresis as a single compound. The phospholipase activity can be separated by affinity chromatography, using a phospholipid analog (PC-Sepharose). The alpha-neurotoxin-like peptide can be separated from the protease inhibitor, Sephadex G-50 gel filtration chromatography can be used, in the presence of high salt (1M NaCl) and alkaline conditions (pH = 8.2). The amino sequence of the protease inhibitor was determined by using the automatic Edman degradation method.
Target
Taicatoxin acts on the voltage-dependent L-type calcium channels from the heart, and on the small conductance Ca2+-activated K+ channels in the
Mode of action
It lowers the plateau of the
Toxicity
A dose of 1 to 2 μg of taicatoxin can kill a mouse of 20 g in 2 hours. Pretreatment with taicatoxin (0.19 μM) on the outer hair cells of guinea pig prevented the cell shortening induced by high K+ (50 mM) and the cell elongation induced by ionomycine (10 μM).[7] This is because taicatoxin blocks the calcium influx through the calcium channels in the cell's membrane. 50 nM of taicatoxin blocks the apamin-sensitive after-hyperpolarizing slow tail K+ currents in rat chromaffin cells, but not immediately; instead, 5 μM of this toxin immediately blocks the ISK(Ca) tail current. It has been shown that taicatoxin blocks the calcium currents in heart cells with IC50 between 10 and 500 nM. Also was seen to evoke severe
References
- PMID 2443275.
- PMID 1485334.
- ^ Universal protein resource accession number Q7LZG2 for "Phospholipase A2 taicatoxin" at UniProt.
- ^ Universal protein resource accession number Q7LZE4 for "Kunitz-type serine protease inhibitor taicotoxin" at UniProt.
- PMID 9242659.
- PMID 12740421.
- ^ S2CID 23849498.
- S2CID 20258431.
External links
- Taicatoxin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)