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.
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). 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.
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.
- 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. doi:10.1073/pnas.91.3.878. PMC . 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.