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.

Source

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] : [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=8302860/ 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] : [http://www.springerlink.com/content/k1y47990y86qvm46/ Block of Voltage-dependent Calcium Channel by the Green Mamba Toxin Calcicludine, Stotz et al., 1999]