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T8024 Sigma

Tetrodotoxin

≥98% (HPLC), powder

Synonym: Fugu poison, Maculotoxin, TTX, Tarichatoxin

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Properties

Related Categories Cell Biology, Cell Signaling and Neuroscience, Fish, Ion Channels, Monovalent Ion Channels,
assay   ≥98% (HPLC)
form   powder
color   white
solubility   dilute citrate or acetate buffer: soluble1 mg/mL (dissolve at pH 4-5. Aqueous solutions, pH 4-5, are stable if stored frozen.)
  strong acid or alkaline solutions: unstable (destroyed by boiling at pH 2.)
storage temp.   2-8°C
Gene Information   rat ... Scnn1g(24768)

Description

Preparation Note

Tetrodotoxin is soluble in dilute citrate or acetate buffer at 1 mg/ml (pH 4-5). Aqueous solutions are stable at pH 4-5 if stored frozen. However, tetrodotoxin is unstable in strong acid or alkaline solutions and is destroyed by boiling at pH2.

Application

Tetrodotoxin has been used as standard during HPLC-based analysis of biotoxins from P. punctata tentacles whole crude extract (PHY-N)1. Tetrodotoxin has also been used to study its effects on low-threshold transient (LTT) Ca2+ currents in rat hippocampal interneurons2.

Biochem/physiol Actions

Reversible, selective blocker of Na+ channels; blocks propagation of impulses in excitable membranes. Used to characterize sodium channels in excitable membranes and to study the role of sodium channels in normal physiology and disease.

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Safety & Documentation

Safety Information

Symbol 
GHS06  GHS06
Signal word 
Danger
Hazard statements 
Precautionary statements 
Hazard Codes (Europe) 
T+
Risk Statements (Europe) 
Safety Statements (Europe) 
22-36/37/39-45
RIDADR 
UN 3462 6.1 / PGI
WGK Germany 
3
RTECS 
IO1450000

Protocols & Articles

Peer-Reviewed Papers

References

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1. The extract of the jellyfish Phyllorhiza punctata promotes neurotoxic effects. Carneiro RF, Nascimento NR, Costa PP, et al. J. Appl. Toxicol. 31(8), 720-9, (2011)

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2. Low-threshold transient calcium current in rat hippocampal lacunosum-moleculare interneurons: kinetics and modulation by neurotransmitters. Fraser DD and MacVicar BA J. Neurosci. 11(9), 2812-20, (1991)

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Rapid single-step induction of functional neurons from human pluripotent stem cells. Zhang Y, Pak C, Han Y, et al. Neuron 78(5), 785-98, (2013)

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A disinhibitory circuit mediates motor integration in the somatosensory cortex. Lee S, Kruglikov I, Huang ZJ, et al. Nat. Neurosci. 16(11), 1662-70, (2013)

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Septo-hippocampal GABAergic signaling across multiple modalities in awake mice. Kaifosh P, Lovett-Barron M, Turi GF, et al. Nat. Neurosci. 16(9), 1182-4, (2013)

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Simultaneous monitoring of presynaptic transmitter release and postsynaptic receptor trafficking reveals an enhancement of presynaptic activity in metabotropic glutamate receptor-mediated long-term depression. Xu W, Tse YC, Dobie FA, et al. J. Neurosci. 33(13), 5867-77, (2013)

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Membrane potential correlates of sensory perception in mouse barrel cortex. Sachidhanandam S, Sreenivasan V, Kyriakatos A, et al. Nat. Neurosci. 16(11), 1671-7, (2013)

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Learning increases intrinsic excitability of hippocampal interneurons. McKay BM, Oh MM, and Disterhoft JF J. Neurosci. 33(13), 5499-506, (2013)

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Antagonism of lidocaine inhibition by open-channel blockers that generate resurgent Na current. Bant JS, Aman TK, and Raman IM J. Neurosci. 33(11), 4976-87, (2013)

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The chemical and evolutionary ecology of tetrodotoxin (TTX) toxicity in terrestrial vertebrates. Hanifin CT Mar. Drugs 8(3), 577-93, (2010)

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Differences in saxitoxin and tetrodotoxin binding revealed by mutagenesis of the Na+ channel outer vestibule. Penzotti, J.L., et al. Biophys. J. 75, 2647, (1998)

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Activity-dependent regulation of tyrosine hydroxylase expression in the enteric nervous system. Chevalier J J. Physiol. 586(7), 1963-75, (2008)

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In vivo synaptic scaling is mediated by GluA2-lacking AMPA receptors in the embryonic spinal cord. Garcia-Bereguiain MA, Gonzalez-Islas C, Lindsly C, et al. J. Neurosci. 33(16), 6791-9, (2013)

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Exposure to cocaine regulates inhibitory synaptic transmission in the nucleus accumbens. Otaka M, Ishikawa M, Lee BR, et al. J. Neurosci. 33(16), 6753-8, (2013)

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The class 4 semaphorin Sema4D promotes the rapid assembly of GABAergic synapses in rodent hippocampus. Kuzirian MS, Moore AR, Staudenmaier EK, et al. J. Neurosci. 33(21), 8961-73, (2013)

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GABAB Receptors Regulate Extrasynaptic GABAA Receptors. Connelly WM, Fyson SJ, Errington AC, et al. J. Neurosci. 33(9), 3780-5, (2013)

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Adaptive evolution of tetrodotoxin resistance in animals. Soong TW and Venkatesh B Trends Genet. 22(11), 621-6, (2006)

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Hypofunction of glutamatergic neurotransmission in the periaqueductal gray contributes to nerve-injury-induced neuropathic pain. Ho YC, Cheng JK, and Chiou LC J. Neurosci. 33(18), 7825-36, (2013)

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Controlling the number of melanopsin-containing retinal ganglion cells by early light exposure. Hong J, Zeng Q, Wang H, et al. Exp. Eye Res. 111, 17-26, (2013)

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Mutation of the protein kinase C site in borna disease virus phosphoprotein abrogates viral interference with neuronal signaling and restores normal synaptic activity. Prat CM PLoS Pathog. 5(5), e1000425, (2009)

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Sodium channels and therapy of central nervous system diseases. Taylor, C.P., and Narasimhan, L.S. Adv. Pharmacol. 39, 47-98, (1997)

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Recent advances in the study of mechanism of action of marine neurotoxins. Narahashi, T., et al. Neurotoxicology 15, 545-554, (1994)

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Tetrodotoxin-resistant sodium channels. Yoshida, S. Cell. Mol. Neurobiol. 14, 227-244, (1994)

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Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Catterall, W.A. Annu. Rev. Pharmacol. Toxicol. 20, 15-43, (1980)

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Tetrodotoxin poisoning outbreak from imported dried puffer fish--Minneapolis, Minnesota, 2014. Cole JB, Heegaard WG, Deeds JR, et al. MMWR Morb. Mortal. Wkly. Rep. 63(51), 1222-5, (2015)

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First report on an inotropic peptide activating tetrodotoxin-sensitive, "neuronal" sodium currents in the heart. Kirchhof P, Tal T, Fabritz L, et al. Circ. Heart Fail. 8(1), 79-88, (2015)

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Is neostigmine effective in severe pufferfish-associated tetrodotoxin poisoning? Liu SH, Tseng CY, and Lin CC Clin. Toxicol. (Phila.) 53(1), 13-21, (2015)

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Genome-wide identification and characterization of functional neuronal activity-dependent enhancers. Malik AN, Vierbuchen T, Hemberg M, et al. Nat. Neurosci. 17(10), 1330-9, (2014)

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GLP-1 and exendin-4 transiently enhance GABAA receptor-mediated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. Korol SV, Jin Z, Babateen O, et al. Diabetes 64(1), 79-89, (2015)

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Tetrodotoxin-resistant voltage-gated sodium channel Nav 1.8 constitutively interacts with ankyrin G. Montersino A, Brachet A, Ferracci G, et al. J. Neurochem. 131(1), 33-41, (2014)

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Overexpression of human mutated G93A SOD1 changes dynamics of the ER mitochondria calcium cycle specifically in mouse embryonic motor neurons. Lautenschläger J, Prell T, Ruhmer J, et al. Exp. Neurol. 247, 91-100, (2013)

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Acute nigro-striatal blockade alters cortico-striatal encoding: an in vivo electrophysiological study. Prosperetti C, Di Giovanni G, Stefani A, et al. Exp. Neurol. 247, 730-6, (2013)

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Neuronal and astroglial correlates underlying spatiotemporal intrinsic optical signal in the rat hippocampal slice. Pál I, Nyitrai G, Kardos J, et al. PLoS ONE 8(3), e57694, (2013)

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Tetrodotoxin as a tool to elucidate sensory transduction mechanisms: the case for the arterial chemoreceptors of the carotid body. Rocher A, Caceres AI, Obeso A, et al. Mar. Drugs 9(12), 2683-704, (2011)

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Tetrodotoxin poisoning. Hwang DF and Noguchi T Adv. Food Nutr. Res. 52, 141-236, (2007)

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Tetrodotoxin-resistant sodium channels in pain. Benham CD Curr. Opin. Pharmacol. 1(1), 91-4, (2001)

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The tetrodotoxin receptor of voltage-gated sodium channels--perspectives from interactions with micro-conotoxins. French RJ, Yoshikami D, Sheets MF, et al. Mar. Drugs 8(7), 2153-61, (2010)

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Sodium channels contribute to degeneration of dorsal root ganglion neurites induced by mitochondrial dysfunction in an in vitro model of axonal injury. Persson AK, Kim I, Zhao P, et al. J. Neurosci. 33(49), 19250-61, (2013)

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Sodium and potassium currents influence Wallerian degeneration of injured Drosophila axons. Mishra B, Carson R, Hume RI, et al. J. Neurosci. 33(48), 18728-39, (2013)

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Functional cooperation of metabotropic adenosine and glutamate receptors regulates postsynaptic plasticity in the cerebellum. Kamikubo Y, Shimomura T, Fujita Y, et al. J. Neurosci. 33(47), 18661-71, (2013)

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Initiation, labile, and stabilization phases of experience-dependent plasticity at neocortical synapses. Wen JA, DeBlois MC, and Barth AL J. Neurosci. 33(19), 8483-93, (2013)

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Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4. Sim S, Antolin S, Lin CW, et al. J. Neurosci. 33(18), 7928-40, (2013)

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Novel GABAergic circuits mediating excitation/inhibition of Cajal-Retzius cells in the developing hippocampus. Quattrocolo G and Maccaferri G J. Neurosci. 33(13), 5486-98, (2013)

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Potentiation of inhibitory synaptic transmission by extracellular ATP in rat suprachiasmatic nuclei. Bhattacharya A, Vavra V, Svobodova I, et al. J. Neurosci. 33(18), 8035-44, (2013)

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Acute suppression of spontaneous neurotransmission drives synaptic potentiation. Nosyreva E, Szabla K, Autry AE, et al. J. Neurosci. 33(16), 6990-7002, (2013)

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Tetrodotoxin (TTX) as a therapeutic agent for pain. Nieto FR, Cobos EJ, Tejada MÁ, et al. Mar. Drugs 10(2), 281-305, (2012)

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Tetrodotoxin: a brief history. Narahashi T Proc. Jpn. Acad.,. Ser. B, Phys. Biol. Sci. 84(5), 147-54, (2008)

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Direction selectivity is computed by active dendritic integration in retinal ganglion cells. Sivyer B and Williams SR Nat. Neurosci. 16(12), 1848-56, (2013)

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Presynaptic NMDA receptor mechanisms for enhancing spontaneous neurotransmitter release. Kunz PA, Roberts AC, and Philpot BD J. Neurosci. 33(18), 7762-9, (2013)

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Rapid, activity-independent turnover of vesicular transmitter content at a mixed glycine/GABA synapse. Apostolides PF and Trussell LO J. Neurosci. 33(11), 4768-81, (2013)

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The molecular mystique of tetrodotoxin. Moczydlowski EG Toxicon 63, 165-83, (2013)

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On the origins and biosynthesis of tetrodotoxin. Chau R, Kalaitzis JA, and Neilan BA Aquat. Toxicol. 104(1-2), 61-72, (2011)

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The tetrodotoxin binding site is within the outer vestibule of the sodium channel. Fozzard HA and Lipkind GM Mar. Drugs 8(2), 219-34, (2010)

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Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity. Korb E, Wilkinson CL, Delgado RN, et al. Nat. Neurosci. 16(7), 874-83, (2013)

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Interleukin-10 down-regulates voltage gated sodium channels in rat dorsal root ganglion neurons. Shen KF, Zhu HQ, Wei XH, et al. Exp. Neurol. 247, 466-75, (2013)

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Behavioral and chemical ecology of marine organisms with respect to tetrodotoxin. Williams BL Mar. Drugs 8(3), 381-98, (2010)

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The infralimbic cortex bidirectionally modulates mesolimbic dopamine neuron activity via distinct neural pathways. Patton MH, Bizup BT, and Grace AA J. Neurosci. 33(43), 16865-73, (2013)

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Presynaptic serotonergic gating of the subthalamonigral glutamatergic projection. Ding S, Li L, and Zhou FM J. Neurosci. 33(11), 4875-85, (2013)

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Mast cell expression of the serotonin1A receptor in guinea pig and human intestine. Wang GD, Wang XY, Zou F, et al. Am. J. Physiol. Gastrointest. Liver Physiol. 304(10), G855-63, (2013)

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5-hydroxytryptamine induced relaxation in the pig urinary bladder neck. Recio P Br. J. Pharmacol. 157(2), 271-80, (2009)

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Over-expression of N-type calcium channels in cortical neurons from a mouse model of Amyotrophic Lateral Sclerosis. Pieri M, Caioli S, Canu N, et al. Exp. Neurol. 247, 349-58, (2013)

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Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B. Priya A, Johar K, and Wong-Riley MT Biochim. Biophys. Acta 1833(12), 2745-56, (2013)

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Self-awareness: how self-peptide/MHC complexes are essential in the development of T cells. Lo WL and Allen PM Mol. Immunol. 55(2), 186-9, (2013)

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Enhancement by interleukin-1β of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons. Liu T, Jiang CY, Fujita T, et al. Mol. Pain 9, 16, (2013)

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Analytical challenges: determination of tetrodotoxin in human urine and plasma by LC-MS/MS. Leung KS, Fong BM, and Tsoi YK Mar. Drugs 9(11), 2291-303, (2011)

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GIRK-like and TRPC-like conductances mediate thyrotropin-releasing hormone-induced increases in excitability in thalamic paraventricular nucleus neurons. Zhang L, Kolaj M, and Renaud LP Neuropharmacology 72, 106-15, (2013)

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The role of tetrodotoxin-resistant sodium channels in pain states: are they the next target for analgesic drugs? Silos-Santiago I Curr. Opin. Investig. Drugs 9(1), 83-9, (2008)

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Tetrodotoxin--distribution and accumulation in aquatic organisms, and cases of human intoxication. Noguchi T and Arakawa O Mar. Drugs 6(2), 220-42, (2008)

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Gustatory detection of tetrodotoxin and saxitoxin, and its competitive inhibition by quinine and strychnine in freshwater fishes. Hara TJ Mar. Drugs 9(11), 2283-90, (2011)

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In vivo recordings of GnRH neuron firing reveal heterogeneity and dependence upon GABAA receptor signaling. Constantin S, Iremonger KJ, and Herbison AE J. Neurosci. 33(22), 9394-401, (2013)

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Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin. Lee CH and Ruben PC Channels (Austin.) 2(6), 407-12, (2008)

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Effects of tetrodotoxin on the mammalian cardiovascular system. Zimmer T Mar. Drugs 8(3), 741-62, (2010)

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Reelin mobilizes a VAMP7-dependent synaptic vesicle pool and selectively augments spontaneous neurotransmission. Bal M, Leitz J, Reese AL, et al. Neuron 80(4), 934-46, (2013)

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Ionic mechanisms of microsecond-scale spike timing in single cells. Markham MR and Zakon HH J. Neurosci. 34(19), 6668-78, (2014)

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The synaptic and circuit mechanisms underlying a change in spatial encoding in the retina. Grimes WN, Schwartz GW, and Rieke F Neuron 82(2), 460-73, (2014)

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Synaptopodin regulates denervation-induced homeostatic synaptic plasticity. Vlachos A, Ikenberg B, Lenz M, et al. Proc. Natl. Acad. Sci. U. S. A. 110(20), 8242-7, (2013)

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Impairment of GABA release in the hippocampus at the time of the first spontaneous seizure in the pilocarpine model of temporal lobe epilepsy. Soukupová M, Binaschi A, Falcicchia C, et al. Exp. Neurol. 257, 39-49, (2014)

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Activity-dependent neurotrophin signaling underlies developmental switch of Ca2+ channel subtypes mediating neurotransmitter release. Miki T, Hirai H, and Takahashi T J. Neurosci. 33(48), 18755-63, (2013)

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Adult neurogenesis produces neurons with unique GABAergic synapses in the olfactory bulb. Valley MT, Henderson LG, Inverso SA, et al. J. Neurosci. 33(37), 14660-5, (2013)

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Influence of obestatin on the gastric longitudinal smooth muscle from mice: mechanical and electrophysiological studies. Squecco R, Garella R, Francini F, et al. Am. J. Physiol. Gastrointest. Liver Physiol. 305(9), G628-37, (2013)

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Taxonomic identity of a tetrodotoxin-accumulating ribbon-worm Cephalothrix simula (Nemertea: Palaeonemertea): a species artificially introduced from the Pacific to Europe. Kajihara H, Sun SC, Chernyshev AV, et al. Zoolog. Sci. 30(11), 985-97, (2013)

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Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination. Nunez-Parra A, Maurer RK, Krahe K, et al. Proc. Natl. Acad. Sci. U. S. A. 110(36), 14777-82, (2013)

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Comparison of the localization of tetrodotoxin between wild pufferfish Takifugu rubripes juveniles and hatchery-reared juveniles with tetrodotoxin administration. Okita K, Takatani T, Nakayasu J, et al. Toxicon 71, 128-33, (2013)

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Synthesis and biological characterization of synthetic analogs of Huwentoxin-IV (Mu-theraphotoxin-Hh2a), a neuronal tetrodotoxin-sensitive sodium channel inhibitor. Deng M, Luo X, Jiang L, et al. Toxicon 71, 57-65, (2013)

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Microbial diversity associated with tetrodotoxin production in marine organisms. Pratheepa V and Vasconcelos V Environ. Toxicol. Pharmacol. 36(3), 1046-54, (2013)

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Evidence for a role of Nav1.6 in facilitating increases in neuronal hyperexcitability during epileptogenesis. Hargus NJ, Nigam A, Bertram EH, et al. J. Neurophysiol. 110(5), 1144-57, (2013)

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Converging effects of a Bifidobacterium and Lactobacillus probiotic strain on mouse intestinal physiology. Lomasney KW, Cryan JF, and Hyland NP Am. J. Physiol. Gastrointest. Liver Physiol. 307(2), G241-7, (2014)

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[Toxicity and toxin profile of scavenging and carnivorous gastropods from the coastal waters of Okinawa Prefecture, Japan]. Taniyama S, Takatani T, Sorimachi T, et al. Shokuhin Eiseigaku Zasshi 54(1), 49-55, (2013)

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Nutritional state-dependent ghrelin activation of vasopressin neurons via retrograde trans-neuronal-glial stimulation of excitatory GABA circuits. Haam J, Halmos KC, Di S, et al. J. Neurosci. 34(18), 6201-13, (2014)

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Stereocontrolled total synthesis of tetrodotoxin from myo-inositol and D-glucose by three routes: aspects for constructing complex multi-functionalized cyclitols with branched-chain structures. Sato K, Akai S, and Yoshimura J Nat. Prod. Commun. 8(7), 987-98, (2013)

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Macroscopic electrical propagation in the guinea pig urinary bladder. Hammad FT, Stephen B, Lubbad L, et al. Am. J. Physiol. Renal Physiol. 307(2), F172-82, (2014)

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Acetylcholine controls GABA-, glutamate-, and glycine-dependent giant depolarizing potentials that govern spontaneous motoneuron activity at the onset of synaptogenesis in the mouse embryonic spinal cord. Czarnecki A, Le Corronc H, Rigato C, et al. J. Neurosci. 34(18), 6389-404, (2014)

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Specialized functions of Nav1.5 and Nav1.9 channels in electrogenesis of myenteric neurons in intact mouse ganglia. Osorio N, Korogod S, and Delmas P J. Neurosci. 34(15), 5233-44, (2014)

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A supercritical density of Na(+) channels ensures fast signaling in GABAergic interneuron axons. Hu H and Jonas P Nat. Neurosci. 17(5), 686-93, (2014)

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Merck 14,9246

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