Calcicludine
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[edit] Summary
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.
[edit] Source
Calcicludine is a toxin in the venom of the green mamba (Dendroaspis angusticeps).
[edit] 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]
[edit] 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]
[edit] 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]
[edit] Toxicity
Calcicludine has been shown to work on rat cardiac hart cells and rat cerebellum granule cells.[1]
[edit] Reference
[1]: Calcicludine, A Venom Peptide of the Kunitz-Type Protease Inhibitor Family, is a Potent Blocker of High-Threshold Ca 2+ Channels with a High Affinity for L-Type Channels in Cerebellar Granule Neurons, Schweitz et al., 1994
[2]: Block of Voltage-dependent Calcium Channel by the Green Mamba Toxin Calcicludine, Stotz et al., 1999
