Taricha granulosa

The Mystery of Tetrodotoxin   

    Of all the naturally produced poison compounds that are found in the world, tetrodotoxin (TTX) is one of the most dangerous and is currently known to be found in seventeen different orders of the biological tree of life (Gall et al. 2012). Gall et al. (2012) suggests three main ideas that attempt to explain how TTX was acquired in vertebrates such as Taricha granulosa. The first idea is that the Rough-skinned Newt incorporates TTX from strains of symbiotic bacteria that can already produce it. The second idea is that TTX toxicity is the result of a buildup of the compound in the newt’s tissues from eating prey that posses TTX. The third and final idea is that tetrodotoxin is produced in the tissues of the Rough-skinned newt (Gall et al. 2012).
A Rough-skinned Newt laying in the moss. Showing his bright underbelly, which signifies his toxicity. Used with permission by Stephen Hart
    Taricha granulosa as a species best fits into the third hypothesis and has been shown to be able to synthesize its own TTX and amazingly without the need for any complex dietary precursor (Hanifin et al. 2002, Gall et al. 2012). This evidence was supported in long-term lab studies where Rough-skinned newts, even when not being fed a diet that contained TTX, were able to maintain and even increase their TTX levels over time as well as replace any excreted toxin (Gall et al. 2012, Moczydlowski 2012). The skin, ovaries, and recently deposited eggs of the Rough-skinned Newt have high amounts toxin while other tissues such as muscle and blood only contain small amounts (Gall et al. 2012). Like any trait, the concentration of TTX in different newt populations can vary largely and is thought to be the result of the newts’ only predator the Garter snake. The Garter snake has co-evolved a resistance to the tetrodotoxin, which forces both species to keep developing stronger toxins and resistances (Hanifin et al. 2002, Gall et al. 2012, Moczydlowski 2012). Another interesting fact of this co-evolution is scientists have found that a Gartner Snake can compare their resistance to a newts’ toxicity when they try to eat it, and will leave prey alone if they think that it might be too toxic to eat (B.C. Frog Watch Program 2013). The picture on the right shows another evolutionary charachteristic of the Rough-skinned Newt that developed with toxicity. The brightly colored underbelly of the newt signifies to other organisms that it is highly poisonous and should not be eaten. Another tactic to limit predation employed by Rough-skinned Newts is the production of toxic eggs which are lethal to most would be predators. In fact the tertrodotoxin found in Taricha granulosa makes it the most poisonous amphibian in the entire Pacific Northwest (B.C. Frog Watch Program 2013).

    With the history of tetrodotoxin established, we can now look at how it functions. The molecule has a very specific effect on animal physiology. TTX targets the Na+ ion channels located in the cell membranes of the nervous system and blocks them from functioning (Moczydlowski 2012). This blockage results in the termination of almost all motor function of the muscles and leads to paralysis of the body (Moczydlowski 2012). Various experiments with this toxin provided some of the first clear evidence for the presence of ion channels inside of cell membranes, which helped to support the theory of nerve action potential (Moczydlowski 2012). TTX functions like a competitive inhibitor, meaning that it blocks the active site of an ion channel from coming into contact and binding with any Na+ molecules. This prevents the creation of the correct electrochemical gradient needed for nerve function. The blockage occurs because the TTX molecule goes through a series of chemical interactions with the active site of the ion channel that hold the molecule firmly in place, preventing proper ion channel function (Moczydlowski 2012). Taricha granulosa newts can display a range of tetrodotoxin from 600 to 26,000 M.U. (Moczydlowski 2012). To put that into perspective, one M.U. is the amount of TTX that is required to kill one adult mouse in only ten minutes (Moczydlowski 2012).  Now it only requires a small amount of TTX to block the ion channels of the cell membrane and with the large amount of toxin that the Rough-skinned Newt holds, it has the ability to kill many would be predators (Moczydlowski 2012).  

    Although the biosynthetic genes for the production of TTX have not yet been found in the newt genome, we can still look towards the possible future of this compound in Medicine (Moczydlowski 2012). Even though tetrodotoxin can be deadly to humans, it does show some promise as a possible drug for use in pain management to treat some conditions of inflammatory and neuropathic pain (Moczydlowski 2012).

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