page_title: Anatoxin-a
section_title: History
hierarchical_section_title: Anatoxin-a / History
caption_attribution_description: Situated on a volcanic hotspot on Africa's Great Rift Valley, lonely Lake Bogoria is a caustic cauldron fringed by geysers and populated by over a million flamingoes. When we visited Bogoria we were the only people there! (Lake Bogoria, Kenya)
context_page_description: Anatoxin-a, also known as Very Fast Death Factor, is a secondary, bicyclic amine alkaloid and cyanotoxin with acute neurotoxicity. It was first discovered in the early 1960s in Canada, and was isolated in 1972. The toxin is produced by seven different genera of cyanobacteria and has been reported in North America, South America, Central America, Europe, Africa, Asia, and Oceania. Symptoms of anatoxin exposure include loss of coordination, muscular fasciculations, convulsions and death by respiratory paralysis. Its mode of action is through the nicotinic acetylcholine receptor where it mimics the binding of the receptor's natural ligand, acetylcholine. As such, anatoxin-a has been used for medicinal purposes to investigate diseases characterized by low acetylcholine levels. Due to its high toxicity and potential presence in drinking water, anatoxin-a poses a threat to animals, including humans. While methods for detection and water treatment exist, scientists have called for more research to improve reliability and efficacy.
context_section_description: Anatoxin-a was first discovered by P.R. Gorham in the early 1960s, after several herds of cattle died as a result of drinking water from Saskatchewan Lake in Ontario, Canada, which contained toxic algal blooms. It was isolated in 1972 by J.P. Devlin from the cyanobacteria Anabaena flos-aquae.
  In 1977, Carmichael, Gorham, and Biggs experimented with anatoxin-a. They introduced toxic cultures of A. flos-aquae into the stomachs of two young male calves, and observed that muscular fasciculations and loss of coordination occurred in a matter of minutes, while death due to respiratory failure occurred anywhere between several minutes and a few hours. They also established that extensive periods of artificial respiration did not allow for detoxification to occur and natural neuromuscular functioning to resume. From these experiments, they calculated that the oral minimum lethal dose (MLD) (of the algae, not the anatoxin molecule), for calves is roughly 420 mg/kg body weight.
  In the same year, Devlin and colleagues discovered the bicyclic secondary amine structure of anatoxin-a. They also performed experiments similar to those of Carmichael et al. on mice. They found that anatoxin-a kills mice 2–5 minutes after intraperitoneal injection preceded by twitching, muscle spasms, paralysis and respiratory arrest. They determined the LD50 for mice to be 250 µg/kg body weight.
  Electrophysiological experiments done by Spivak et al. (1980) on frogs showed that anatoxin-a is a potent agonist of the muscle-type α12βγδ nAChR. Anatoxin-a induced depolarizing neuromuscular blockade, contracture of the frog's rectus abdominis muscle, depolarization of the frog sartorius muscle, desensitization, and alteration of the action potential. Later, Thomas et al., (1993) through his work with chicken α4β2 nAChR subunits expressed on mouse M 10 cells and chicken α7 nAChR expressed in oocytes from Xenopus laevis, showed that anatoxin-a is also a potent agonist of neuronal nAChR.
  Many cases of wildlife and livestock deaths due to anatoxin-a 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, and in Ireland in 1997 and 2005. 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 anatoxin-a have been reported in the United States, Canada, and Finland between 1980 and the present.
  A particularly interesting case of anatoxin-a 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.
caption: Flamingos at Lake Bogoria
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