The Neuromuscular Junction
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
The drug hemicholinium-3 inhibits the reuptake of choline at the presynaptic terminal, which depresses ACh synthesis because most of the choline needed for ACh synthesis is provided through reuptake of the choline resulting from hydrolysis of ACh in the synaptic cleft, and only a relatively small amount of choline is transported from the cell body. α-latrotoxin is an extremely potent neurotoxin, that is a poison of the nervous system, contained in the venom of the black widow spider. It causes massive exocytosis of ACh from presynaptic terminals either by forming open pores in the presynaptic membrane that allow the influx of Ca2+ and Na+ or by binding to special receptors, thereby initiating processes that lead to exocytosis. The depletion of ACh eventually leads to muscle paralysis. Botulinum toxin, produced by a bacterium found in poisoned foods, is one of the most toxic substances known. Only 2 ng of a form of this toxin, when injected intravenously, can kill a human adult by preventing ACh vesicles from fusing with the presynaptic membrane and releasing ACh into the synaptic cleft. Extremely small doses of other forms of this toxin, commercially known as Botox, are injected into the skin to relax muscles causing wrinkles. Botox is also used in the treatment of disorders caused by overactive muscle movement or conditions arising from hyperactivity of some nerves.
Principles of Treatment for Arthropod Bites, Stings, and Other Exposure
Gail Miriam Moraru, Jerome Goddard in The Goddard Guide to Arthropods of Medical Importance, Seventh Edition, 2019
Widow spiders and some scorpions produce ill effects in humans by neurotoxic venoms. The primary toxin in widow spider (Latrodectus spp.) venom is α-latrotoxin which binds to specific presynaptic receptors (neurexin 1a and CIRL), precipitating neurotransmitter release, particularly norepinephrine and acetylcholine.13 This leads to sweating, piloerection, muscular spasm, weakness, tremor, and sometimes paralysis, stupor, and convulsions. This type of venom may not produce obvious skin lesions but will primarily produce these systemic reactions.
Clinical Toxicology of Spider Bites
Jürg Meier, Julian White in Handbook of: Clinical Toxicology of Animal Venoms and Poisons, 2017
Only the actions of alpha latrotoxin, which is the neurotoxin active against mammalian tissues, are of relevance in human envenomation, although some of the other venom fractions are of relevance in non-clinical research. Alpha latrotoxin is a potent stimulator of release of transmitter substances from neurons throughout the nervous system. Thus it causes depletion of synaptic vesicles and an initial increase in mepps coresponding to releases of the transmitter acetyl choline at the vertebrate neuromuscular junction, equating to a variable presynaptic blockade and consequent patchy paralysis of voluntary muscle44,110-113. Similarly it has been shown to cause depletion of the transmitter catecholamines at adrenergic nerve endings in the autonomic nervous system113,114, and stimulation of release of the transmitters acetylcholine, norepinephrine, and gamma amino butyric acid from brain synaptosomes116,117. It also appears to have similar actions at sensory nerve terminals118. Alpha latrotoxin has been shown to increase the permeability of lipid bilayer membranes by forming ionic channels119, and it has been suggested that it stimulates transmitter release by both increasing nerve ending permeability to cations and directly stimulating release by a process of redistribution of membrane components, possibly also inhibiting vesicle recycling120. The membrane effects of the venom appear specific to neuronal tissue, suggesting either a differential toxic binding by specific cell types or differential responses of cells to uniformly bound toxin110,119, although the apparent concentration of the toxin in neural tissue may suggest the former121.
Venomous bites during pregnancy: the black widow spider (Latrodectus mactans)
Published in Toxin Reviews, 2019
Gianmarco Troiano, Alessandra Bagnoli, Astrid Mercone, Nicola Nante
Widow venom contains α-latrotoxin, which provokes a massive presynaptic release of acetylcholine. Latrotoxin and latrodectin selectively interact with latrophilin and neurexin receptors in the lipid bilayer membrane of presynaptic terminals, resulting in the formation of cation channels allowing an influx of Ca2+ into the cell. Toxin activity causes the release of a large amount of such neurotransmitters as noradrenaline and acetylcholine, as well as calcium-independent gamma-aminobutyric acid, and has an important effect on the neuromuscular junction (Sotelo-Cruz and Gomez-Rivera 2016). After a person has been bitten, crampy muscle spasms usually occur within an hour in the chest (upper extremity bites) or the abdomen (lower extremity bites). The pain may be intense enough to mimic myocardial infarction or acute abdomen, but it is rarely life threatening and typically resolves within 48–72 h (Clark et al.1992, Juckett 2013). Nausea, weakness, local or generalized diaphoresis, and facial edema may occur (Clark et al.1992).
Black widow spider bite in Johannesburg
Published in Southern African Journal of Infectious Diseases, 2018
Teressa Sumy Thomas, Alan Kemp, Kim Pieton Roberg
α-latrotoxin is a neurotransmitter found within black widow venom that binds non-specifically to neuronal presynaptic receptors within the peripheral nervous system. This causes massive release of neurotransmitters, especially acetylcholine and noradrenaline, resulting in the clinical symptoms observed. The toxin is unable to cross the blood–brain barrier, hence no central nervous system symptoms are observed.1
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