Taicatoxin (TCX) is a snake
toxinthat 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 taipansnake, 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 venomgland of the snake.cite journal | author = Brown AM, Yatani A, Lacerda AE, Gurrola GB, Possani LD | title = Neurotoxins that act selectively on voltage-dependent cardiac calcium channels | journal = Circ. Res. | volume = 61 | issue = 4 Pt 2 | pages = I6–9 | year = 1987 | pmid = 2443275 | doi = | issn = ]
SDS-PAGEanalysis, TCX (CAS|112154-17-3) was determined to be a complex held together by non-covalent forces of the following three polypeptides in a stoichiometryof 1:1:4 respectively:cite journal | author = Possani LD, Martin BM, Yatani A, Mochca-Morales J, Zamudio FZ, Gurrola GB, Brown AM | title = Isolation and physiological characterization of taicatoxin, a complex toxin with specific effects on calcium channels | journal = Toxicon | volume = 30 | issue = 11 | pages = 1343–64 | year = 1992 | pmid = 1485334 | doi = | issn = ]
* a α-
neurotoxin-like peptide(8 kDa),
* a neurotoxic
phospholipase(16 kDa; UniProt|Q7LZG2), and
serine protease inhibitor(7 kDa; UniProt|Q7LZE4).
The active complex was isolated by ion exchange
chromatographythrough 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 electrophoresisas 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 degradationmethod.
Taicatoxin acts on the voltage-dependent L-type calcium channels from the heart, and on the small conductance Ca2+-activated K+ channels in the
chromaffin cellsand in the brain.cite journal | author = Doorty KB, Bevan S, Wadsworth JD, Strong PN | title = A novel small conductance Ca2+-activated K+ channel blocker from Oxyuranus scutellatus taipan venom. Re-evaluation of taicatoxin as a selective Ca2+ channel probe | journal = J. Biol. Chem. | volume = 272 | issue = 32 | pages = 19925–30 | year = 1997 | pmid = 9242659 | doi = 10.1074/jbc.272.32.19925 | issn = ] It has a high affinity for the 125I- apaminacceptor-binding sites of the rat synaptosomal membranes (Ki = 1.45±0.22 nM) and blocks affinity-labeling of a 33-kDa 125I-apamin-binding polypeptide. Other neurotoxins that act on the calcium channels are calcicludine, calciseptine, ω- conotoxin, ω- agatoxin.
Mode of action
It lowers the plateau of the
action potential, decreasing the duration and the concentration parameters in the heart muscle cells. It has been seen that the 16-kDa subunit exhibits phospholipase activity, inducing a release of acyl CoA and acyl carnitine, fact which has a negative effect on cell’s integrity and function. TCX is involved in the outer hair cell motilitytoo, by blocking the calcium traffic and preventing the cell shortening and elongation.cite journal | author = Schnee ME, Ricci AJ | title = Biophysical and pharmacological characterization of voltage-gated calcium currents in turtle auditory hair cells | journal = J. Physiol. (Lond.) | volume = 549 | issue = Pt 3 | pages = 697–717 | year = 2003 | pmid = 12740421 | doi = 10.1113/jphysiol.2002.037481 | issn = ] cite journal | author = Su MC, Lee SY, Tan CT, Su CC, Li SY, Lin RH, Hung CC, Lin MJ | title = Taicatoxin inhibits the calcium-dependent slow motility of mammalian outer hair cells | journal = Hear. Res. | volume = 203 | issue = 1-2 | pages = 172–9 | year = 2005 | pmid = 15855042 | doi = 10.1016/j.heares.2004.12.003 | issn = ] Taicatoxin has an inhibitory effect by reducing the affinity of 125I-apamin for its acceptor and not by alteration of the acceptor binding site density.
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 pigprevented the cell shortening induced by high K+ (50 mM) and the cell elongation induced by ionomycine (10 μM). 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 10-500 nM. Also was seen to evoke severe arrhythmiasand prolonged changes in the intercellular electrical coupling.cite journal | author = Fantini E, Athias P, Tirosh R, Pinson A | title = Effect of TaiCatoxin (TCX) on the electrophysiological, mechanical and biochemical characteristics of spontaneously beating ventricular cardiomyocytes | journal = Mol. Cell. Biochem. | volume = 160-161 | issue = | pages = 61–6 | year = 1996 | pmid = 8901456 | doi = 10.1007/BF00240032 | issn = ]
Wikimedia Foundation. 2010.
Look at other dictionaries:
taicatoxin — Complex oligomeric protein toxin from Oxyuranus scutelatus scutelatus. Blocks high but not low threshold calcium channels of heart muscle. The oligomer contains a neurotoxin like peptide (8 kD), a phospholipase (16 kD) and a serine protease… … Dictionary of molecular biology
Neurotoxin — A neurotoxin is a toxin that acts specifically on nerve cells (neurons), usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue.… … Wikipedia
Toxin — This article is about the class of poisonous substances. For other uses, see Toxin (disambiguation). Universal warning symbol used to indicate toxic substances or environments A toxin (from Ancient Greek: τοξικόν toxikon) is a poisonous… … Wikipedia
Botulinum toxin — Clinical data Pregnancy cat. ? Legal status ? (US) Rout … Wikipedia
Lipopolysaccharide — Structure of a lipopolysaccharide Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram negative bacteria, act… … Wikipedia
Psychoactive toad — is a name used for toads from which psychoactive substances from the family of bufotoxins can be derived. The skin and poison of Bufo alvarius (Colorado River toad or Sonoran Desert toad) contain 5 MeO DMT and bufotenin. Other species contain… … Wikipedia
Mycotoxin — A mycotoxin (from Greek μύκης (mykes, mukos) “fungus” and Latin (toxicum) “poison”) is a toxic secondary metabolite produced by organisms of the fungus kingdom, commonly known as molds. The term ‘mycotoxin’ is usually reserved for the … Wikipedia
Taipan — This article is about the Australian snake. For other uses, see Tai Pan (disambiguation). Taipans Inland Taipan (Oxyuranus microlepidotus) Scientific classification … Wikipedia
Charybdotoxin — Refined model of Charybdotoxin Identifiers Symbol ? … Wikipedia
Poison dart frog — Poison dart frogs (Dendrobatidae) Dendrobates azureus (top) and Dendrobates leucomelas Scientific classification … Wikipedia