Calcicludine
Encyclopedia
Calcicludine is a protein toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 from the venom of the green mamba
Green mamba
Green mamba may refer to:* Eastern green mamba* Western 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
Green mamba
Green mamba may refer to:* Eastern green mamba* Western green mamba...

 (Dendroaspis angusticeps).

Chemistry

Calcicludine is a 60-amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 polypeptide with six cysteines forming three disulfide bridges. Calcicludine structurally resembles dendrotoxin
Dendrotoxin
Dendrotoxins are a class of neurotoxins produced by mamba snakes that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions...

, but works differently, since even at high concentrations, calcicludine has no effect on dendrotoxin-sensitive potassium channels 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 to the L-type calcium channel (IC50
IC50
The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...

 = 88nM[2]). However, sensitivity
Sensitivity
Stimulus|Sensitivity may refer to:* Sensitivity , the ability to react to a stimulus* Sensitivity , the strength of physical or emotional reaction in people* Sensitivity , variations in process dynamics and control systems...

 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
Granule cell
In neuroscience, granule cells refer to tiny neurons that are around 10 micrometres in diameter. Granule cells are found within the granular layer of the cerebellum , the dentate gyrus of the...

 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.
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