Calcicludine
Calcicludine (CaC) is a protein toxin from the venom of the green mamba that inhibits high-voltage-activated calcium channels, especially L-type calcium channels.
Sources
Calcicludine is a toxin in the venom of the green mamba (Dendroaspis angusticeps).
Chemistry
Calcicludine is a 60-amino acid polypeptide with six cysteines forming three disulfide bridges. Calcicludine structurally resembles dendrotoxin, but works differently, since even at high concentrations, calcicludine has no effect on dendrotoxin-sensitive potassium channels in chicken and rat neurons.[1]
Target
Calcicludine is a blocker of high-voltage-activated calcium channels (L-, N- and P-type channels). It has highest affinity to the L-type calcium channel (IC50 = 88nM[2]). However, sensitivity of the drug on the channel depends on the species and the tissue. For example, the IC50 for block of L-type calcium channels on a cerebellar granule cell is 0.2 nM, but the IC50 of the block of rat peripheral DRG neuronal L-type channels is around 60-80 nM.[1]
Mode of Action
Calcicludine has a unique mode of action, which is still incompletely understood. It has been suggested to act by a partial pore block or an effect on channel gating.[2]
Toxicity
Calcicludine has been shown to work on rat cardiac cells and rat cerebellum granule cells.[1]
References
- ^ a b c Schweitz H, Heurteaux C, Bois P, Moinier D, Romey G, Lazdunski M (February 1994). "Calcicludine, a venom peptide of the Kunitz-type protease inhibitor family, is a potent blocker of high-threshold Ca2+ channels with a high affinity for L-type channels in cerebellar granule neurons". Proc Natl Acad Sci USA. 91 (3): 878–82. Bibcode:1994PNAS...91..878S. doi:10.1073/pnas.91.3.878. PMC 521415. PMID 8302860.
- ^ Stotz SC, Spaetgens RL, Zamponi GW (March 2000). "Block of voltage-dependent calcium channel by the green mamba toxin calcicludine". J. Membr. Biol. 174 (2): 157–65. doi:10.1007/s002320001040. PMID 10742459. S2CID 20776129. Archived from the original on 2000-09-15. Retrieved 2009-02-06.
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- Toxins
- cardiotoxin
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toxins
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Virulence factor |
- Aflatoxin
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- beta-Nitropropionic acid
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toxins
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toxins
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- note: some toxins are produced by lower species and pass through intermediate species
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