Sodium channel tetrodotoxin. Medical search. Frequent questions

Puffer fish contain the potent neurotoxin tetrodotoxin. (medscape.com)
It contains tetrodotoxin, a potent neurotoxin that affects the nervous system. (govegan.recipes)
Lunartail puffer ( Lagocephalus lunaris ) is a toxic fish, containing a potent neurotoxin known as tetrodotoxin (TTX). (thedynamicnature.com)

Alpha subunits, such as SCN11A, mediate voltage-dependent gating and conductance, while auxiliary beta subunits regulate the kinetic properties of the channel and facilitate membrane localization of the complex. (wikipedia.org)
Mammalian sodium channels are heterotrimers, composed of a central, pore-forming alpha subunit and two auxiliary beta subunits. (thermofisher.com)
Sodium channels in the adult central nervous system and heart contain beta 1 through beta 4 subunits, whereas sodium channels in adult skeletal muscle have only the beta 1 subunit. (thermofisher.com)
This conclusion was also verified by immunostaining for voltage-gated sodium channel alpha subunits and by direct dual soma/axonal recordings. (elsevierpure.com)

Poisoning with the neurotoxin tetrodotoxin (TTX) occurs after ingestion of various species of puffer fish (see the image below). (medscape.com)
Despite the small size of these octopuses-12 to 20 cm (5 to 8 in)-and their relatively docile nature, the blue-ringed octopuses are dangerous to humans when handled and provoked because of their venom that contains the powerful neurotoxin tetrodotoxin. (animalofthings.com)

Multiple saxitoxin-binding sites in bullfrog muscle: tetrodotoxin-sensitive sodium channels and tetrodotoxin-insensitive sites of unknown function. (aspetjournals.org)
Characterization of saxitoxin- and tetrodotoxin-induced channel closures. (uchicago.edu)
To date, lab members have employed these versatile oxidation technologies to prepare natural products that include manzacidin A and C, agelastatin, tetrodotoxin, and saxitoxin. (stanford.edu)
Access to toxins and modified forms thereof (including saxitoxin, gonyautoxin, batrachotoxin, and veratridine) through de novo synthesis drives studies to elucidate toxin-receptor interactions and to develop new pharmacologic tools to study ion channel function in primary cells and murine pain models. (stanford.edu)
Site 1 sodium channel blockers such as tetrodotoxin and saxitoxin are small-molecule drugs with powerful local anesthetic properties. (childrenshospital.org)
Although tetrodotoxin and saxitoxin were the test anesthetics, the approach could potentially be applied to other drug delivery systems. (childrenshospital.org)

The model uses a sodium channel blocker, tetrodotoxin (TTX), that is infused into the hippocampus of rodents. (medscape.com)
Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than controls after tetrodotoxin (TTX, a sodium channel blocker that inhibits axonal action potentials). (jefferson.edu)
Sodium channel blocker, available with or without citrate. (bosunlife.com)
INTRODUCTION: Tetrodotoxin (TTX) is a potent sodium channel blocker, with significant neurotoxicity, found in marine animals like pufferfish and blue-ringed octopus. (cdc.gov)

Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. (xenbase.org)

The Swarm was able to record pseudo-action potentials stably across all 24 objectives and provided pharmacological characterization of diverse sodium channel blockers. (frontiersin.org)
BACKGROUND: Chemical permeation enhancers (CPEs) have the potential to improve nerve blockade by site 1 sodium channel blockers such as tetrodotoxin (TTX). (anesthesiaexperts.com)
CPEs may be useful in enhancing nerve blockade from site 1 sodium channel blockers. (anesthesiaexperts.com)

Here, we investigated the efficacy and toxicity of CPE-enhanced nerve blockade across a range of TTX concentrations using 2 CPEs (sodium octyl sulfate and octyl trimethyl ammonium bromide). (anesthesiaexperts.com)

It is a heterocyclic, small, organic molecule that acts directly on the electrically active sodium channel in nerve tissue (see the image below). (medscape.com)
Contactin/F3, a cell adhesion molecule, has been shown to interact with and enhance surface expression of sodium channels Na v 1.2 and Na v 1.9. (jneurosci.org)
With this in mind, and zeroing in on one particular molecule, called tetrodotoxin, we can weave together a fascinating narrative of cultures, fads, ceremonies, word-choice, and basic natural history. (zooatlanta.org)
This work is enabled in part through the advent of small molecule modulators of channel function. (stanford.edu)
Small molecule toxins serve as lead compounds for the design of isoform-selective channel modulators, affinity reagents, and fluorescence imaging probes. (stanford.edu)
Each set of peptides binds one tetrodotoxin molecule. (childrenshospital.org)

Little is known about the neuronal voltage-gated sodium channels (NaVs) that control neurotransmission in the parasympathetic nervous system. (johnshopkins.edu)
It is the uncharged form of the anesthetic (RN) which is able to cross the neuronal membrane and block the sodium/potassium channel which conducts nerve activity. (cornerstoneendo.com)

Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel protein which is encoded by the SCN11A gene on chromosome 3 in humans. (wikipedia.org)
Medical records of an 8-year-old boy with PEM were analyzed retrospectively, which included clinical characteristics, follow-up information, and SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9) gene analysis. (frontiersin.org)
To address the question of specificity for the allele encoding the Na V 1.4-R669H variant as a cause of HypoPP and to produce a model system in which to characterize functional defects of the mutant channel and susceptibility to paralysis, we generated knockin mice carrying the ortholog of the gene encoding the Na V 1.4-R669H variant (referred to herein as R669H mice). (jci.org)
Gene expression analysis showed that that NaV 1.7 was virtually the only tetrodotoxin-sensitive NaV1 gene expressed in guinea pig and human airway parasympathetic ganglia, where mouse ganglia expressed NaV1.1, 1.3, and 1.7. (johnshopkins.edu)
Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)
The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. (utsouthwestern.edu)

A rat brain Na+ channel alpha subunit with novel gating properties. (xenbase.org)
Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. (xenbase.org)

This channel is largely expressed in small-diameter nociceptors of the dorsal root ganglion and trigeminal ganglion neurons, but is also found in intrinsic myenteric neurons. (wikipedia.org)
The upregulation of voltage-gated sodium channel Na v 1.3 has been linked to hyperexcitability of axotomized dorsal root ganglion (DRG) neurons, which underlies neuropathic pain. (jneurosci.org)
Notably, genetic deletion of Na V 1.1 in sensory neurons caused profound and visible motor coordination deficits in conditional knockout mice of both sexes, similar to conditional Piezo2-knockout animals, suggesting that this channel is a major contributor to sensory proprioceptive transmission. (elifesciences.org)
This article provides insight into the importance of a voltage-gated sodium channel in proprioceptors, a group of mechanosensory neurons that target muscle. (elifesciences.org)
The sodium current underlying action potentials in guinea pig hippocampal CA1 neurons. (xenbase.org)
Nav1.7 amplifies weak stimuli in neurons and acts as a threshold channel for firing action potentials [ 3 , 4 ]. (biomedcentral.com)

NaV channels are activated in response to depolarization and selectively allow flow of Na+ ions. (thermofisher.com)
These sodium channels cyclically pump sodium ions into and out of the muscle cell, causing contraction and relaxation of the cell. (zooatlanta.org)
Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo. (xenbase.org)
Ions , such as sodium (Na + ) and chloride (Cl - ), have an even more difficult time going through the membrane than glucose . (visionlearning.com)

The NaV channels are classified into two groups according to their sensitivity to tetrodotoxin (TTX): TTX-sensitive (NaV1.1, NaV1.2, NaV1.3, NaV1.4, NaV1.6 and NaV1.7) and TTX-resistant (NaV1.5, NaV1.8 and NaV1.9). (thermofisher.com)
To evaluate the Swarm screening system, we optimized a series of heterologous optogenetic spiking HEK293 cell assays for several voltage-gated sodium channel subtypes including Nav1.2, Nav1.5, and Nav1.7. (frontiersin.org)

Tetrodotoxin interferes with the transmission of signals from nerves to muscles and causes an increasing paralysis of the muscles of the body. (cdc.gov)
Tetrodotoxin is extremely potent and can cause death by paralysis. (discovermagazine.com)
Tetrodotoxin blocks sodium channels, leading to paralysis and interfering with nerve signals. (govegan.recipes)
Their venom contains tetrodotoxin, which can cause muscle weakness, paralysis, and respiratory failure in humans. (govegan.recipes)

This property is found in similar channels, namely Nav1.8, and has been associated with slower channel kinetics than the tetrodotoxin-sensitive sodium channels. (wikipedia.org)
Topical menthol blocks both Nav1.8 and Nav1.9 channels in the dorsal root ganglion. (wikipedia.org)
2009. Isoflurane inhibits the tetrodotoxin-resistant voltage-gated sodium channel Nav1.8. . (cornell.edu)

Tetrodotoxin is an extremely potent poison (toxin) found mainly in the liver and sex organs (gonads) of some fish, such as puffer fish, globefish, and toadfish (order Tetraodontiformes) and in some amphibian, octopus, and shellfish species. (cdc.gov)

however, its ability to regulate sodium channel 1.7 (Nav1.7), a key driver of temporomandibular joint (TMJ) hypernociception, remains unknown. (biomedcentral.com)

Tetrodotoxin acts on the central and the peripheral nervous systems (ie, autonomic, motor, sensory nerves). (medscape.com)

Voltage-gated sodium channels are membrane protein complexes that play a fundamental role in the rising phase of the action potential in most excitable cells. (wikipedia.org)
Functional modulation of brain sodium channels by protein kinase C phosphorylation. (xenbase.org)

Voltage-gated sodium channels mediate a rapid and transient increase in Na + permeability in response to membrane depolarization, thereby contributing to the generation and conduction of action potentials. (jneurosci.org)
Voltage-gated sodium channels are dynamic membrane proteins essential for signaling in nervous and muscular systems. (bbk.ac.uk)

The tetrodotoxin inhibition of epibatidine-induced contractions in Decentralized and ObNT-Reinn suggests a relocation of nicotinic receptors from nerve terminals to more distant axonal sites, perhaps as a compensatory mechanism to recover bladder function. (jefferson.edu)

Following depolarization of the cell, voltage-gated sodium channels become inactivated through a change in conformation in which the 4th segments in each domain move into the pore region in response to the highly positive voltage expressed at the peak of the action potential. (wikipedia.org)
Tetrodotoxin blocks diffusion of sodium through the sodium channel, thus preventing depolarization and propagation of action potentials in nerve cells. (medscape.com)

Menthol inhibits action potentials by dampening the Na+ channel activity without affecting normal neural activity in the affected area. (wikipedia.org)
2007. Isoflurane inhibits NaChBac, a prokaryotic voltage-gated sodium channel. . (cornell.edu)

Tissue injury may alter the composition, distribution, and activity of sodium channels on nociceptors. (cornerstoneendo.com)

Sodium channels and gating currents. (xenbase.org)

Biophysical and molecular mechanisms of Shaker potassium channel inactivation. (xenbase.org)

Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. (bvsalud.org)

Much of this work has focused on studies of eukaryotic Na and Cl ion channels. (stanford.edu)
Charalambous, Kalypso and O'Reilly, Andrias O. and Bullough, P.A. and Wallace, Bonnie A. (2009) Thermal and chemical unfolding and refolding of a eukaryotic sodium channel. (bbk.ac.uk)

The 4th transmembrane segment of each domain is the voltage-sensing region of the channel. (wikipedia.org)
These results suggest that tetrodotoxin-resistant voltage gated sodium channels are involved in the development and maintenance of bone cancer pain. (wikipedia.org)
Voltage-gated sodium channels (NaV) are essential for the generation of action potentials and for cell excitability. (thermofisher.com)
Brevetoxins are a suite of marine neurotoxins that activate voltage-gated sodium channels (VGSCs) in cell membranes, with toxicity occurring from persistent activation of the channel at high doses. (mdpi.com)
A neutral amino acid change in segment IIS4 dramatically alters the gating properties of the voltage-dependent sodium channel. (xenbase.org)
Structure and function of voltage-gated sodium and calcium channels. (xenbase.org)
A voltage-dependent gating transition induces use-dependent block by tetrodotoxin of rat IIA sodium channels expressed in Xenopus oocytes. (xenbase.org)
Dysregulation of voltage-gated sodium channels (Na v s) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. (biomedcentral.com)
In a second program area, the Du Bois group is exploring voltage-gated ion channel structure and function using the tools of chemistry in combination with those of molecular biology, electrophysiology, microscopy and mass spectrometry. (stanford.edu)
2009. Comparative effects of halogenated inhaled anesthetics on voltage-gated Na+ channel function. . (cornell.edu)
2007. Isoform-selective effects of isoflurane on voltage-gated Na+ channels. . (cornell.edu)
2003. Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals. . (cornell.edu)
The nanofibers carry two peptides (shown as arrays of blue and violet dots) that are modified from peptides on tetrodotoxins' natural binding site on voltage-gated sodium channels. (childrenshospital.org)
Janiszewski L. The action of toxins on the voltage-gated sodium channel. (cdc.gov)

Tetrodotoxin (TTX) is an extraordinarily powerful toxin that binds to sodium channels in the nerves of animals. (zooatlanta.org)
Binds preferentially to Na+ channels in their inactivated state. (ncats.io)
when tetrodotoxin is delivered to the nerve, it binds simultaneously to both peptides. (childrenshospital.org)
When this nanostructure is injected near the target nerve, the tetrodotoxin slowly releases by diffusion and other processes, and binds to P1 and P2 on the nerve itself. (childrenshospital.org)

TTX selectively blocks the ion transport of the sodium channel. (thedynamicnature.com)

A second area of interest focuses on the role of ion channels in electrical conduction and the specific involvement of channel subtypes in the sensation of pain. (stanford.edu)

In Nav1.9, this is mostly associated with the slower speed at which channel inactivation occurs. (wikipedia.org)
Food: Exposure to tetrodotoxin usually occurs through eating improperly prepared fish or possibly through contamination of other food products. (cdc.gov)
Exposure occurs due to ingestion of fish or other food containing tetrodotoxin. (cdc.gov)

A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. (xenbase.org)
These results demonstrate an essential role of Phe-1489 in Na(+)-channel inactivation. (xenbase.org)
It is proposed that the hydrophobic cluster of Ile-1488, Phe-1489, and Met-1490 serves as a hydrophobic latch that stabilizes the inactivated state in a hinged-lid mechanism of Na(+)-channel inactivation. (xenbase.org)
Inactivation of the sodium channel. (xenbase.org)
Destruction of sodium conductance inactivation in squid axons perfused with pronase. (xenbase.org)
Amino acid residues required for fast Na(+)-channel inactivation: charge neutralizations and deletions in the III-IV linker. (xenbase.org)
Destruction of the sodium conductance inactivation by a specific protease in perfused nerve fibres from Loligo. (xenbase.org)
Structural parts involved in activation and inactivation of the sodium channel. (xenbase.org)

These adapted peptides bind to tetrodotoxin (shown as gold hexagons) and release it when the nanofibers are injected near the nerve, providing prolonged local anesthesia. (childrenshospital.org)
This caused the resulting molecules to assemble themselves into nanostructures with the two peptides positioned together, mimicking the way they're positioned on the sodium channel. (childrenshospital.org)
This schematic shows the peptides P1 and P2 with hydrophobic modifications that enable them to self-assemble into nanostructures that bind to tetrodotoxin (TTX). (childrenshospital.org)
Think of the peptides like hands - if you're trying to catch tetrodotoxin, you need two hands to come together to hold it. (childrenshospital.org)

The toxic dose is not clear because puffer fish have different concentrations of tetrodotoxin. (medscape.com)
Detection of tetrodotoxins in European bivalve shellfish have been reported in the Netherlands, United Kingdom, France, Greece, and Italy, although concentrations were low in comparison to published minimum lethal doses for humans. (medscape.com)
At some concentrations, the addition of sodium octyl sulfate increased the duration of block from TTX plus epinephrine, and epinephrine increased that from TTX plus CPEs. (anesthesiaexperts.com)

In control bladder strips, since tetrodotoxin did not inhibit epibatidine contractions, nicotinic receptors are likely located on nerve terminals. (jefferson.edu)

Though most sodium channels are blocked by tetrodotoxin, Nav1.9 is tetrodotoxin-resistant due to the presence of serine on an extracellular linker that plays a role in the selectivity of the pore for Na+. (wikipedia.org)
Of the nine distinct channel isoforms described (Na v 1.1 to Na v 1.9), Na v 1.5, Na v 1.8 and Na v 1.9 are resistant to tetrodotoxin (TTX). (biomedcentral.com)
One type of sodium channel is the TTX (tetrodotoxin) resistant channel. (cornerstoneendo.com)
These sodium channels have been shown to increase in the presence of prostaglandins (a potent inflammatory mediator) and may cause the sodium channel to be resistant to dental anesthetics. (cornerstoneendo.com)
The proteins appear to be remarkably resistant to either type of treatment, with "denatured" channels, retaining significant helical secondary structure even at 77 °C or in 10% SDS. (bbk.ac.uk)
These studies suggest that whilst sodium channels must be sufficiently flexible to undergo major conformational changes during their functional cycle, the proteins are highly resistant to unfolding, a feature that is important for maintaining structural integrity during dynamic processes. (bbk.ac.uk)

Because of this role in altering the threshold potential, Nav1.9 is considered a threshold channel. (wikipedia.org)

Recent studies show that essential oils are emerging as a promising source for modulation of the GABAergic system and sodium ion channels. (mdpi.com)

The correctly refolded channels were capable of undergoing the toxin-induced conformational change indicative of ligand binding. (bbk.ac.uk)

Tetrodotoxin interferes with the transmission of signals from nerves to muscles by blocking sodium channels. (medscape.com)
The team then put the tetrodotoxin-bearing nanostructures to the test, injecting them near the sciatic nerves of live rats. (childrenshospital.org)

This conclusion was suggested by phase plot analysis of somatic action potentials and by local tetrodotoxin application to the axon and somatodendritic compartments. (elsevierpure.com)

RNAscope analysis and in vitro patch-clamp recordings in genetically identified mouse proprioceptors show ubiquitous channel expression and significant contributions to intrinsic excitability. (elifesciences.org)

The packaged anesthetics stayed in place longer than free tetrodotoxin, with no toxic tissue reaction, and neurobehavioral tests in the animals showed that the nerve block lasted for as long as 16 hours. (childrenshospital.org)

As would be expected from previous studies, tetrodotoxin potently blocked the parasympathetic responses in the airways of each species. (johnshopkins.edu)

It works by blocking sodium channels, which are necessary for the contraction of muscles like the diaphragm that control breathing. (discovermagazine.com)

Chemical structure of tetrodotoxin. (medscape.com)
In this study circular dichroism spectroscopy was used to investigate the changes in secondary structure accompanying chemical and thermal denaturation of detergent-solubilised sodium channels isolated from Electrophorus electricus electroplax. (bbk.ac.uk)

Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)

A molecular view of neurotransmitter receptors and ionic channels. (xenbase.org)

Indoor Air: Because the natural source of tetrodotoxin is from living organisms, and manufacturing tetrodotoxin artificially in appreciable quantities is extremely difficult, dissemination through indoor air is unlikely. (cdc.gov)

Anatomy32

Organisms22

Diseases9

Chemicals and Drugs149

Analytical, Diagnostic and Therapeutic Techniques and Equipment9

Phenomena and Processes29

Disciplines and Occupations2

Technology, Industry, Agriculture1

Information Science3

Potent neurotoxin3

Subunits4

Neurotoxin tetrodotoxin2

Saxitoxin6

Blocker4

Skeletal muscle sodium1

Blockers3

Blockade1

Molecule6

Neuronal2

Gene6

Subunit2

Neurons6

Ions4

NaV1.22

Paralysis4

Nav1.83

Extremely potent1

NaV1.71

Sensory1

Protein2

Membrane2

Inhibition1

Depolarization2

Inhibits2

Nociceptors1

Currents1

Potassium channel1

Cardiac1

Eukaryotic2

Voltage14

Binds4

Selectively1

Subtypes1

Occurs3

Inactivation8

Peptides4

Concentrations3

Nerve terminals1

Resistant6

Threshold channel1

Modulation1

Conformational change1

Nerves2

Action1

Intrinsic1

Toxic1

Species1

Muscles1

Chemical2

Functional1

Molecular1

Natural1