Effects Laboratory studies using mice showed that characteristic effects of acute<unk>  poisoning via intraperitoneal injection include muscle fasciculations, tremors, staggering, gasping, respiratory paralysis, and death within minutes. Zebrafish exposed to<unk>  contaminated water had altered heart rates. There have been cases of non-lethal poisoning in humans who have ingested water from streams and lakes that contain various genera of cyanobacteria that are capable of producing<unk> . The effects of non-lethal poisoning were primarily gastrointestinal: nausea, vomiting, diarrhea, and abdominal pain. A case of lethal poisoning was reported in Wisconsin after a teen jumped into a pond contaminated with cyanobacteria. Exposure routes Oral Ingestion of drinking water or recreational water that is contaminated with<unk>  can pose fatal consequences since<unk>  was found to be quickly absorbed through the gastrointestinal tract in animal studies. Dozens of cases of animal deaths due to ingestion of<unk>  contaminated water from lakes or rivers have been recorded, and it is suspected to have also been the cause of death of one human. One study found that<unk>  is capable of binding to acetylcholine receptors and inducing toxic effects with concentrations in the nano-molar (nM) range if ingested. Dermal Dermal exposure is the most likely form of contact with cyanotoxins in the environment. Recreational exposure to river, stream, and lake waters contaminated with algal blooms has been known to cause skin irritation and rashes. The first study that looked at in vitro cytotoxic effects of<unk>  on human skin cell proliferation and migration found that<unk>  exerted no effect at 0.1 µg/mL or 1 µg/mL, and a weak toxic effect at 10 µg/mL only after an extended period of contact (48 hours). Inhalation No data on inhalation toxicity of<unk>  is currently available, though severe respiratory distress occurred in a water skier after they inhaled water spray containing a fellow cyanobacterial neurotoxin, saxitoxin. It is possible that inhalation of water spray containing<unk>  could pose similar consequences. Mechanism of toxicity<unk>  is an agonist of both neuronal α4β2 and α4 nicotinic acetylcholine receptors present in the CNS as well as the (α1)2βγδ muscle-type nAchRs that are present at the neuromuscular junction.<unk>  has an affinity for these muscle-type receptors that is about 20 times greater than that of acetylcholine.) However, the cyanotoxin has little effect on muscarinic acetylcholine receptors; it has a 100 fold lesser selectivity for these types of receptors than it has for nAchRs.<unk>  also shows much less potency in the CNS than in neuromuscular junctions. In hippocampal and brain stem neurons, a 5 to 10 times greater concentration of<unk>  was necessary to activate nAchRs than what was required in the PNS. In normal circumstances, acetylcholine binds to nAchRs in the post-synaptic neuronal membrane, causing a conformational change in the extracellular domain of the receptor which in turn opens the channel pore. This allows Na+ and Ca2+ ions to move into the neuron, causing cell depolarization and inducing the generation of action potentials, which allows for muscle contraction. The acetylcholine neurotransmitter then dissociates from the nAchR, where it is rapidly cleaved into acetate and choline by acetylcholinesterase. The effects of<unk>  on nicotinic acetylcholine receptors at the neuromuscular junction<unk>  binding to these nAchRs cause the same effects in neurons. However,<unk>  binding is irreversible, and the<unk>  nAchR complex cannot be broken down by acetylcholinesterase. Thus, the nAchR is temporarily locked open and after a period of time becomes desensitized. In this desensitized state the nAchRs no longer let cations pass through, which ultimately leads to a blockage of neuromuscular transmission. Two enantiomers of<unk> , the positive enantiomer, (+)-anatoxin-a, is 150 fold more potent than the synthetic negative enantiomer, (−)-anatoxin-a. This is because (+)-anatoxin-a, the s-cis enone conformation, has a distance a 6.0 Å between its nitrogen and carbonyl group, which corresponds well to the 5.9 Å distance that separate the nitrogen and oxygen in acetylcholine. Respiratory arrest, which results in a lack of an oxygen supply to the brain, is the most evident and lethal effect of<unk> . Injections of mice, rats, birds, dogs, and calves with lethal doses of<unk>  have demonstrated that death is preceded by a sequence of muscle fasciculations, decreased movement, collapse, exaggerated abdominal breathing, cyanosis and convulsions. In mice,<unk>  also seriously impacted blood pressure and heart rate, and caused severe acidosis. Cases of toxicity Many cases of wildlife and livestock deaths due to<unk>  have been reported since its discovery. Domestic dog deaths due to the cyanotoxin, as determined by analysis of stomach contents, have been observed at the lower North Island in New Zealand in 2005, in eastern France in 2003, in California of the United States in 2002 and 2006, in Scotland in 1992, in Ireland in 1997 and 2005, in Germany in 2017 an 2020 In each case the dogs began showing muscle convulsions within minutes, and were dead within a matter of hours. Numerous cattle fatalities arising from the consumption of water contaminated with cyanobacteria that produce<unk>  have been reported in the United States, Canada, and Finland between 1980 and the present. Flamingos at Lake Bogoria A particularly interesting case of<unk>  poisoning is that of lesser flamingos at Lake Bogoria in Kenya. The cyanotoxin, which was identified in the stomachs and fecal pellets of the birds, killed roughly 30,000 flamingos in the second half of 1999, and continues to cause mass fatalities annually, devastating the flamingo population. The toxin is introduced into the birds via water contaminated with cyanobacterial mat communities that arise from the hot springs in the lake bed.
Anatoxin-a
Satratoxin-H
Muscarinic toxin 7
Charybdotoxin
Α-Bungarotoxin
Alpha-neurotoxin
Brevetoxin
Bungarotoxin