Biology: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
- ↑ 1.0 1.1 1.2 "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. February 1994. doi:10.1073/pnas.91.3.878. PMID 8302860. Bibcode: 1994PNAS...91..878S.
- ↑ "Block of voltage-dependent calcium channel by the green mamba toxin calcicludine". J. Membr. Biol. 174 (2): 157–65. March 2000. doi:10.1007/s002320001040. PMID 10742459. http://link.springer-ny.com/link/service/journals/00232/bibs/0174002/01740157.html. Retrieved 2009-02-06.
 |  |
