Overview

Brief Summary

Tetrodotoxin

Chemical Structure

Tetrodotoxin is a weakly basic, low molecular weight (319.27 Da) neurotoxin, consisting of a positively charged and poisonous guanidinium moiety. Existing as a zwitterion in acidic solutions, tetrodotoxin is highly polar as a result of the abundance of OH and NH groups. The particularly potent neurotoxin is a selective inhibitor of voltage-gated sodium channels (VGSCs), leading to symptoms of numbness, paralysis, and hypotension, as well as ultimately death (Chau et al., 2011).

Biogenic Origins

First isolated from the pufferfish of the genus Tetraodontidae. tetrodotoxin has since been found in a variety of other species, including newts of the genus Taricha, toads of the genus Atelopus, octopuses of the genus Hapalochlaena, and sea stars of the genus Astropecten. In fact, since its initial discovery, the presence of tetrodotoxin has been reported in at least six phyla of organisms, including the Chordata, Mollusca, Echinodermata, Chaetognatha, Arthropoda, and Platyhelminthes (Chau et al., 2011). The wide distribution of the neurotoxin amongst unrelated species has led to the emergence of different theories regarding the biogenic origins of the molecule.

A possible explanation for the origin of tetrodotoxin is that it is a product of a bacterium, acquired via the food chain or by bacterial symbiosis, a mutualistic relationship existing between bacteria and other organisms. Particularly common in marine animals, the symbiotic bacteria live within organs where the conditions are optimum for the production of secondary metabolites, which are ultimately used by the host organism for chemical defence (Chau et al., 2011). Supporting the theory of bacterial symbiosis is the vast variety of tetrodotoxin-producing bacteria, which have been isolated from the large variety of species reported to contain the neurotoxin. For instance, species of the bacterium genus Vibrio have been found to occur in Atergatis floridus (Noguchi et al., 1983), Fugu vermicularis vermicularis (Noguchi et al., 1987), Fugu vermicularis radialis (Lee et al., 2000), Hapalochlaena maculosa (Hwang et al., 1989), Astropecten polyacanthus (Narita et al., 1987), Nassarius semiplicatus (Wang et al., 2008), and Niotha clathrata (Cheng et al., 1995). However, no evidence of symbiotic bacteria has been found in newts, thus demanding explanations of non-bacterial origin (Chau et al., 2011).

Mode of Action

Tetrodotoxin binds to amino acid residues on receptor site 1 of voltage-gated sodium channels (VGSCs). As key proteins in the initiation and propagation of action potentials, VGSCs are abundant in many different types of tissue. However, there exist nine different VGSC subtypes in mammals, each with distinct properties, and as a result, certain VGSC subtypes are more sensitive to tetrodotoxin than others  (Nieto et al., 2012). The extent to which tetrodotoxin is able to block each VGSC subtype depends on its concentration; while nanomolar concentrations are sufficient to block subtypes Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.6, and Nav1.7, micromolar concentrations are required for Nav1.5, Nav1.8, and Nav1.9 (Nieto et al., 2012).

By blocking VGSCs, tetrodotoxin is able to reduce the permeability of sodium ions in axon membranes without affecting the diffusion of potassium ions, thereby blocking the transmission of signals from the central nervous system  (Fuhrman, 1967). It is this inhibition of the ion channel and interference with conduction that ultimately leads to paralysis, a common symptom of tetrodotoxin poisoning.

Potential Therapeutic Use

VGSCs are essential components of nociception due to the transmission of nerve impulses depending largely on the protein. However, as each VGSC subtype has specific properties and thus contributes to a specific type of pain, it is essential that drugs be produced to block each channel selectively. Due to tetrodotoxin being a selective blocker of the protein, its potential to be used as a painkiller has been researched extensively. Nevertheless, before it can be used as a common local anaesthetic, it must be made more selective for specific VGSC subtypes (Fuhrman, 1967). 

  • Chau, R., Kalaitzis, J.A., Neilan, B.A., 2011. On the origins and biosynthesis of tetrodotoxin. Aquatic Toxicology. 104, 61-72.
  • Cheng, C.A., Hwang, D.F., Tsai, Y.H., Chen, H.C., Jeng, S.S., Noguchi, T., Ohwada, K., Hashimoto, K., 1995. Microflora and tetrodotoxin-producing bacteria in a gastropod, Niotha clathrata. Food Chem. Toxicol. 33, 929–934.
  • Fuhrman, F.A., 1967. Tetrodotoxin. Scientific American. 217(2):60-71.
  • Hwang, D., Arakawa, O., Saito, T., Noguchi, T., Simidu, U., Tsukamoto, K., Shida, Y., Hashimoto, K., 1989. Tetrodotoxin-producing bacteria from the blue-ringed octopus Octopus maculosus. Mar. Biol. 100, 327–332.
  • Lee, M., Jeong, D., Kim, W., Kim, H., Kim, C., Park, W., Park, Y., Kim, K., Kim, H., Kim, D., 2000. A tetrodotoxin-producing Vibrio strain, LM-1, from the puffer fish Fugu vermicularis radiatus. Appl. Environ. Microbiol. 66, 1698.
  • Narita, H., Matsubara, S., Miwa, N., Akahane, S., Murakami, M., Goto, T., Nara, M., Noguchi, T., Saito, T., Shida, Y., 1987. Vibrio alginolyticus, a TTX-producing bacterium isolated from the starfish Astropecten polyacanthus. Nippon Suisan Gakk. 53, 617–621.
  • Nieto, F.R., Cobos, E.J., Tejada, M.A., Sánchez-Fernández, C., González-Cano, R., Cendán, C.M., 2012. Tetrodotoxin (TTX) as a Therapeutic Agent for Pain. Mar. Drugs. 10, 281-305.
  • Noguchi, T., Hwang, D., Arakawa, O., Sugita, H., Deguchi, Y., Shida, Y., Hashimoto, K., 1987. Vibrio alginolyticus, a tetrodotoxin-producing bacterium, in the intestines of the fish Fugu vermicularis vermicularis. Mar. Biol. 94, 625–630.
  • Noguchi, T., Uzu, A., Koyama, K., Hashimoto, K., 1983. Occurrence of tetrodotoxin as the major toxin in xanthid crab Atergatis floridus. Bull. Jpn. Soc. Sci. Fish. 49, 1887–1892.
  • Wang, X., Yu, R., Luo, X., Zhou, M., Lin, X., 2008. Toxin-screening and identification of bacteria isolated from highly toxic marine gastropod Nassarius semiplicatus. Toxicon 52, 55–61.
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Distribution

Indo-Pacific. Found most commonly in the tidal rock pools along the southern coast of Australia.

(Moynihan 1985. Sea World Inc 1996. Rogerson 1998)

Biogeographic Regions: australian (Native ); indian ocean (Native ); pacific ocean (Native )

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Physical Description

Morphology

The blue-ringed octopus is a small octopus that ranges in size from 4 mm at birth to up to 20 cm in adulthood. It is dark brown to dark yellow/ tan-yellow in coloring. The most outstanding characteristic of this species is the iridescent blue rings in the eye spots. These rings are reported to "glow" when an individual is aggravated.

(Campbell 1998. Rogerson 1998. Hanlon and Messenger 1996)

Average mass: 26 g.

Other Physical Features: ectothermic ; bilateral symmetry

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Ecology

Habitat

Most commonly found in rocky, shallow pools of water or in shallow corals. Also found under rocks in sandy or muddy stretches of bottom where alga is plentiful. Particularly common after storms when it can be found looking for crabs and bivalves.

(Moynihan 1985, Campbell 1998, Australian wildlife lectures 1998, Rogerson 1998, Park 1987)

Aquatic Biomes: coastal

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coastal; highly toxic
  • UNESCO-IOC Register of Marine Organisms
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Depth range based on 35 specimens in 1 taxon.
Water temperature and chemistry ranges based on 5 samples.

Environmental ranges
  Depth range (m): 0 - 55
  Temperature range (°C): 14.610 - 26.692
  Nitrate (umol/L): 0.565 - 1.945
  Salinity (PPS): 35.037 - 35.479
  Oxygen (ml/l): 4.657 - 5.625
  Phosphate (umol/l): 0.120 - 0.276
  Silicate (umol/l): 0.983 - 1.528

Graphical representation

Depth range (m): 0 - 55

Temperature range (°C): 14.610 - 26.692

Nitrate (umol/L): 0.565 - 1.945

Salinity (PPS): 35.037 - 35.479

Oxygen (ml/l): 4.657 - 5.625

Phosphate (umol/l): 0.120 - 0.276

Silicate (umol/l): 0.983 - 1.528
 
Note: this information has not been validated. Check this *note*. Your feedback is most welcome.

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Trophic Strategy

At one week of age, the blue ringed octopus will begin to eat crab pieces. As the octopus matures, it will begin to eat live crabs and bivalve mollusks. The octopus will either entice its prey into its vicinity and inject a poison into the water that will paralyze it or will inject the poison into its prey directly. It is also believed that the octopus will capture prey, forming an airtight pouch around it, and inserting the poison into the pouch, cause the prey to take the poison in through its respiratory system. The poison is a neurotoxin which causes paralysis, which is particularly fatal if the poison affects either the heart or repiratory system. To date there is no antitoxin. Generally though, humans are not considered prey to this creature and a bite from one seems to be more of a defensive response than anything else.

References: Boyle 1987. Microsoft 1993. Loadsman and Thompson 2000. Park 1987. Berry 1998.

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Life History and Behavior

Reproduction

The female will initiate reproduction by specific coloring and posturing. The male will then approach her to begin courtship. Courtship consists of "love play" (Wood, 1999) and caressing. The male will then use the hectocotylus, a modified arm consisting of a groove between the suckers and ending in a spoonlike tip, to deposit the sperm in the female's oviduct, which is located under the mantle. Shortly thereafter, the female will begin to lay her eggs and the brooding period will begin. Characteristic brooding of this species is for the female to carry the eggs in its arms. She will guard them for a period of fifty days, at which point they will hatch into planktonic "paralarva". Initially at birth, the octopus will be only 4 mm long. This stage of the life cycle, the young will float to the top and join the plankton for about a month. At the end of this time period they will once again return to the bottom to resume their normal life.

(Microsoft 1993. Boyle 1987. Wood 1999. Hanlon and Messenger 1996)

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Molecular Biology and Genetics

Molecular Biology

Barcode data: Hapalochlaena maculosa

The following is a representative barcode sequence, the centroid of all available sequences for this species.


There are 2 barcode sequences available from BOLD and GenBank.

Below is a sequence of the barcode region Cytochrome oxidase subunit 1 (COI or COX1) from a member of the species.

See the BOLD taxonomy browser for more complete information about this specimen and other sequences.

ACTTTATATTTTATTTTTGGAATTTGATCAGGTTTATTAGGTACTTCTTTA---AGATTAATAATTCGAACAGAATTAGGACAACCAGGATCTTTACTTAATGAC---GATCAATTATATAATGTAATTGTCACTGCTCATGCATTTGTAATAATTTTTTTTCTAGTTATACCTGTAATAATTGGGGGTTTTGGAAATTGATTAGTTCCTTTAATA---TTAGGAGCCCCTGATATAGCATTTCCTCGAATAAATAATATAAGATTTTGATTACTTCCCCCTTCCTTAACTTTTTTACTTTCATCAGCAGCAGTAGAAAGAGGAGCTGGTACAGGATGAACAGTTTATCCTCCCTTATCTAGAAATTTAGCCCATATAGGACCATCTGTTGATTTA---GCAATTTTTTCTTTACATTTAGCAGGAATTTCCTCAATTTTAGGAGCTATTAATTTTATTACCACTATTATTAATATACGATGAGAAGGTATATTAATAGAACGACTACCTTTATTTGTTTGATCTGTATTTATTACAGCTTTTTTATTATTATTATCTTTACCTGTATTTGCAGGG---GCTATTACTATTCTTTTAACTGATCGAAATTTTAATACTACATTTTTTGATCCTAGAGGAGGAGGAGATCCTATTTTATATCAACATTTA------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------TTT
-- end --

Download FASTA File

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Statistics of barcoding coverage: Hapalochlaena maculosa

Barcode of Life Data Systems (BOLDS) Stats
Public Records: 3
Specimens with Barcodes: 5
Species With Barcodes: 1
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Conservation

Conservation Status

There was no information on conservation efforts made for the blue-ringed octopus. A problem has begun to arise surrounding the publicity of the toxicity of its venom. People have begun to over-react and kill octopuses encountered in shallow tidal pools.

(Park 1987)

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Relevance to Humans and Ecosystems

Benefits

This species is considered one of the most dangerous animals in the sea because of the toxicity of its venom. In addition, the bite of the blue-ringed octopus is not painful. Therefore, there have been reported cases where people handled one and did not realize they had been bitten until the symptons of envenomation began to occur.

(Australian Wildlife Lectures 1998, Seaworld 1996, Park 1987)

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This species lacks an ink sac and therefore has become a common addition to the marine aquarium. This is much to the dismay of many toxicologists who feel that people selling and buying them are uninformed of the true danger they pose. This species also is used for its venom. One of Australia's major industries is its venom industry, in which the blue-ringed octopus plays a valuable role.

 In addition this species has come under study to provide information on the mantle and the microscopic protrusions on the mantle of cephalopods.

(Hanlon and Messenger 1996. Parks 1987. Wood 1999)

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Wikipedia

Southern blue-ringed octopus

The southern blue-ringed octopus (Hapalochlaena maculosa) is one of three (or perhaps four) species of blue-ringed octopuses. It is most commonly found in tidal rock pools along the south coast of Australia. As an adult, it can grow up to 20 centimetres (8 in) long (top of the mantle to the tip of the arms) and on average weighs 26 grams (0.9 oz). They are normally a docile species, but they are highly venomous possessing venom capable of killing humans. Their blue rings appear with greater intensity when they become aggravated or threatened.[citation needed]

References[edit]

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