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. A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low MAMBA stands for Mobile Artillery Monitoring Battlefield Asset, a Counter-battery radar operated by the Royal Artillery. A Calcium channel is an Ion channel which displays selective permeabiltiy to Calcium ions
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Source
Calcicludine is a toxin in the venom of the green mamba (Dendroaspis angusticeps). MAMBA stands for Mobile Artillery Monitoring Battlefield Asset, a Counter-battery radar operated by the Royal Artillery. The eastern green mamba or common mamba ( Dendroaspis angusticeps) is a venomous Arboreal snake indigenous to the eastern side of southern Africa
Chemistry
Calcicludine is a 60-amino acid polypeptide with six cysteines forming three disulfide bridges. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino 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. Dendrotoxins are a class of Neurotoxins produced by Mamba Snakes ( Dendroapsis) that block particular subtypes of Voltage-gated In the field of Cell biology, potassium channels are the most widely distributed type of Ion channel and are found in virtually all living organisms Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information [1]
Target
Calcicludine is a blocker of high-voltage-activated calcium channels (L-, N- and P-type channels). A Calcium channel is an Ion channel which displays selective permeabiltiy to Calcium ions It has highest affinity to the L-type calcium channel (IC50 = 88nM[2]). The IC50 is a measure of the effectiveness of a compound in inhibiting biological or biochemical function 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. Granular cell also refers to Juxtaglomerular cell in the kidney In Neuroscience, granule cells refer to tiny neurons (a type of 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. Granular cell also refers to Juxtaglomerular cell in the kidney In Neuroscience, granule cells refer to tiny neurons (a type of [1]
References
[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
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