calcicludine
{{Short description|Snake venom toxin}}
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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.
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.{{cite journal |vauthors=Schweitz H, Heurteaux C, Bois P, Moinier D, Romey G, Lazdunski M |title=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 |journal=Proc Natl Acad Sci USA |volume=91 |issue=3 |pages=878–82 |date=February 1994 |pmid=8302860 |pmc=521415 |doi=10.1073/pnas.91.3.878|bibcode=1994PNAS...91..878S |doi-access=free }}
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.{{cite journal |vauthors=Stotz SC, Spaetgens RL, Zamponi GW |title=Block of voltage-dependent calcium channel by the green mamba toxin calcicludine |journal=J. Membr. Biol. |volume=174 |issue=2 |pages=157–65 |date=March 2000 |pmid=10742459 |doi=10.1007/s002320001040 |s2cid=20776129 |url=http://link.springer-ny.com/link/service/journals/00232/bibs/0174002/01740157.html |access-date=2009-02-06 |archive-url=https://web.archive.org/web/20000915111057/http://link.springer-ny.com/link/service/journals/00232/bibs/0174002/01740157.html |archive-date=2000-09-15 |url-status=dead }}
Toxicity
Calcicludine has been shown to work on rat cardiac cells and rat cerebellum granule cells.