Calcicludine (CaC) is a protein

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...

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 The eastern green mamba (''Dendroaspis angusticeps'') is a highly venomous snake species of the mamba genus ''Dendroaspis'' native to the coastal regions of southern East Africa. Species description, Described by Scottish people, Scottish surgeon ...

)''.

Chemistry

Calcicludine is a 60-

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

polypeptide with six cysteines forming three disulfide bridges. Calcicludine structurally resembles

dendrotoxin Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes ('' Dendroaspis'') that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctio ...

, 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 cel ...

in chicken and rat neurons.

Target

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

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

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 A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granul ...

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 A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granul ...

References

{{Toxins Dendroaspis Neurotoxins Vertebrate toxins Ion channel toxins