Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Tetrodotoxin TTX , one of the most toxic substances in nature, is present in bacteria, invertebrates, fishes, and amphibians.
Marine organisms seem to bioaccumulate TTX from their food or acquire it from symbiotic bacteria, but its origin in amphibians is unclear. Taricha granulosa can exhibit high TTX levels, presumably concentrated in skin poison glands, acting as an agent of selection upon predatory garter snakes Thamnophis. This co-evolutionary arms race induces variation in T. Using morphology and biochemistry, we investigated differences in toxin localization and quality between two populations at the extremes of toxicity.
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TTX concentration within poison glands is related to the volume of a single cell type in which TTX occurs exclusively in distinctive secretory granules, suggesting a relationship between granule structure and chemical composition. TTX was detected in mucous glands in both populations, contradicting the general understanding that these glands do not secrete defensive chemicals and expanding currently held interpretations of amphibian skin gland functionality.
Skin secretions of the two populations differed in low-mass molecules and proteins. Our results demonstrate that interpopulation variation in TTX levels is related to poison gland morphology. Tetrodotoxin TTX is one of the most toxic and well-studied but still mysterious natural products. TTX selectively binds to voltage-gated sodium channels in muscle and nerve tissues, causing paralysis and death 1. It was first isolated from pufferfish Tetraodontidae but is now known to be distributed across a vast diversity of organisms.
Among eukaryotes, it has been identified in distantly related invertebrates, including dinoflagellates, flatworms, bivalves, gastropods, sea slugs, crabs, starfish, and octopuses, and vertebrates, where it is restricted to amphibians and fishes 1 , 2 , 3.
