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Neuropeptide Receptor-Ion Channel Coupling in the Mammalian Brain
Published in Gerard O’Cuinn, Metabolism of Brain Peptides, 2020
Voltage-clamp experiments in brain slice preparations have revealed that activation of the CCKA receptor reduces a potassium current to excite raphe neurones28. The potassium current involved is not dependent on extracellular calcium, since the inward current produced by CCK was not affected by removal of calcium ions or by the calcium-dependent channel blockers, charybdotoxin (100nM) and apamin (100nM). The response was unaffected by blockers of IA(dendrotoxin 100–300nM) or inward rectifier currents (rubidium, 5mM; cesium, 2mM) but was blocked by barium (1–2mM).
Overview of Ion Channels, Antiepileptic Drugs, and Seizures
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Potassium channels are ubiquitous in eukaryotic cells and exhibit more diverse characteristics than channels for other ions.22 Over a dozen types of K+ channels have already been identified using variations on the patch clamp technique.2 Selective toxins also have been discovered that potently block particular types of K+ channels, which allow examination of the role of the particular current type in controlling the excitability pattern of specific cell types.23 These agents include apamin, a toxin from the honey bee, that inhibits Ca2+-activated K+ channels. Two scorpion toxins, charybdotoxin and noxioustoxin, and a toxin from mamba snake venom, dendrotoxin, also selectively affect different K+ channels.23 G-proteins act to couple many types of K+ channel to neurotransmitters.24
Biology and Distribution of Venomous Snakes of Medical Importance and The Composition of Snake Venoms
Published in Jürg Meier, Julian White, Handbook of: Clinical Toxicology of Animal Venoms and Poisons, 2017
Three groups of snake neurotoxins acting at the presynaptic level have to be distinguished: the PLA2-toxins, the dendrotoxins and the fasciculins (see Figure 7). All PLA2-toxins found in elapid and some viperid snake venoms have a basic phospholipase A2 in common that may be complexed with acidic, basic or neutral protein units. PLA2-Toxins may consist of a single chain (e.g. Caudoxin from Bitis caudalis venom, Notexin from Notechis scutatus venom, Ammodytoxin from Vipera ammodytes venom), of two chains (β-Bungarotoxin from Bungarus multicinctus venom), they may form a two protein complex (e.g. Crotoxin from Crotalus durissus terrificus venom, Mojave toxin from Crotalus scutulatus venom) or they may consist of a multiple protein complex (e.g. Taipoxin from Oxyuranus scutellatus venom, Textilotoxin from Pseudonaja textilis venom). They all act in a complex, usually triphasic manner55,56,70. Probably due to their binding at the presynaptic nerve membrane, a short inhibition of neurotransmitter release is observed. In a second phase there is an increasing neurotransmitter release due to the action of the phospholipase, finally followed by a block, when all neurotransmitter is released74. For crotoxin, a two component neurotoxin, it has been shown that the non-enzymatic component A increases the pharmacological efficacy of the PLA2-component B, since component A directs component B onto its acceptor at the neuromuscular junctions. In so doing component A prevents the PLA2-component B from being bound onto inefficient binding sites249. For detailed reviews on PLA2-toxins, see 82,85. Dendrotoxins are very basic single chain polypeptides consisting of 57 to 60 amino acid residues, cross-linked by three disulphide bridges. They are devoid of enzymatic activity and block certain potassium channels in nerve membranes, thus facilitating the release of neurotransmitters (for a review, see86). Dendrotoxins have only been found in venoms of the African mambas (Dendroaspis species). Dendrotoxins share structural homology with the bovine pancreatic trypsin inhibitor (aprotinin, BPTI), although they neither inhibit trypsin nor other trypsin-like serine proteinases. Fasciculins are again neurotoxins, which are only found in Mamba venoms (Dendroaspis species). They belong to a toxin group, which was named “angusticeps-type" toxins (from Dendroaspis angusticeps, the Common Mamba). These toxins share structural homology with postsynaptic neurotoxins and snake cardiotoxins, although they are immunologically distinct from all other snake toxins. Fasciculins are potent inhibitors of cholineesterases from different sources. Therefore, they potentiate the action of acetylcholine and cause a generalized muscle fasciculation in vivo (for a review, see87).
In vitro discovery of a human monoclonal antibody that neutralizes lethality of cobra snake venom
Published in mAbs, 2022
Line Ledsgaard, Andreas H. Laustsen, Urska Pus, Jack Wade, Pedro Villar, Kim Boddum, Peter Slavny, Edward W. Masters, Ana S. Arias, Saioa Oscoz, Daniel T. Griffiths, Alice M. Luther, Majken Lindholm, Rachael A. Leah, Marie Sofie Møller, Hanif Ali, John McCafferty, Bruno Lomonte, José M. Gutiérrez, Aneesh Karatt-Vellatt
In the experiments, an nAChR-mediated current was elicited by 70 µM acetylcholine (ACh, Sigma-Aldrich), approximately the EC80 value, and after compound wash-out, 2 U acetylcholinesterase (Sigma-Aldrich) was added to ensure complete ACh removal. The ACh response was allowed to stabilize over three ACh additions, before the fourth addition was used to evaluate the effect of α-cobratoxin (4 nM α-cobratoxin, reducing the ACh response by 80%), preincubated with varying concentrations of IgGs. α-cobratoxin and IgGs were preincubated at room temperature for at least 30 minutes before application, and the patched cells were preincubated with α-cobratoxin and IgG for 5 minutes prior to the fourth ACh addition. As a negative control, an IgG specific to dendrotoxins was included.