Calcicludine (CaC) is a protein

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

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 Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of ...

in chicken and rat

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

Target

Calcicludine is a blocker of high-voltage-activated calcium channels (L-, N- and P-type channels). It has highest

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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 The name granule cell has been used for a number of different types of neurons whose only common feature is that they all have very small cell bodies. Granule cells are found within the granular layer of the cerebellum, the dentate gyrus of t ...

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.

Toxicity

Calcicludine has been shown to work on rat cardiac cells and rat cerebellum granule cells.

References

{{Toxins Dendroaspis Neurotoxins Snake toxins Ion channel toxins Calcium channel blockers