المؤلفون: Xi-Yao Gu¹, Ben-Long Liu¹, Kai-Kai Zang1¹, Liu Yang¹, Hua Xu², Hai-Li Pan³, Zhi-Qi Zhao¹, Yu-Qiu Zhang¹ yuqiuzhang@fudan.edu.cn

المصدر: Molecular Brain. 2015, Vol. 8 Issue 1, p1-11. 11p.

مصطلحات موضوعية: *NEUROTOXIC agents, *TETRODOTOXIN, *NERVE cell culture, *NERVOUS system, *ION channels

مستخلص: Background: Systemically administered dexmedetomidine (DEX), a selective α2 adrenergic receptor (α2-AR) agonists, produces analgesia and sedation. Peripherally restricted α2-AR antagonist could block the analgesic effect of systemic DEX on neuropathic pain, with no effect on sedation, indicating peripheral analgesic effect of DEX. Tetrodotoxinresistant (TTX-R) sodium channel Nav1.8 play important roles in the conduction of nociceptive sensation. Both α2-AR and Nav1.8 are found in small nociceptive DRG neurons. We, therefore, investigated the effects of DEX on the Nav1.8 currents in acutely dissociated small-diameter DRG neurons. Results: Whole-cell patch-clamp recordings demonstrated that DEX concentration-dependently suppressed TTX-R Nav1.8 currents in small-diameter lumbar DRG neurons. DEX also shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction and increased the threshold of action potential and decrease electrical and chemical stimuli-evoked firings in small-diameter DRG neurons. The α2-AR antagonist yohimbine or α2A-AR antagonist BRL44408 but not α2B-AR antagonist imiloxan blocked the inhibition of Nav1.8 currents by DEX. Immunohistochemistry results showed that Nav1.8 was predominantly expressed in peripherin-positive small-diameter DRG neurons, and some of them were α2A-AR-positive ones. Our electrophysiological recordings also demonstrated that DEX-induced inhibition of Nav1.8 currents was prevented by intracellular application of G-protein inhibitor GDPβ-s or Gi/o proteins inhibitor pertussis toxin (PTX), and bath application of adenylate cyclase (AC) activator forskolin or membrane-permeable cAMP analogue 8-Bromo-cAMP (8-Br-cAMP). PKA inhibitor Rp-cAMP could mimic DEX-induced inhibition of Nav1.8 currents. Conclusions: We established a functional link between α2-AR and Nav1.8 in primary sensory neurons utilizing the Gi/o/AC/cAMP/PKA pathway, which probably mediating peripheral analgesia of DEX. [ABSTRACT FROM AUTHOR]

المؤلفون: Pristerà, Alessandro¹, Baker, Mark D.^2,3, Okuse, Kenji¹ k.okuse@imperial.ac.uk, Spafford, J. David⁴

المصدر: PLoS ONE. Aug2012, Vol. 7 Issue 8, Special section p1-16. 16p.

مصطلحات موضوعية: *SODIUM channels, *TETRODOTOXIN, *NEURONS, *CELLS, *NERVOUS system, *AXONS

مستخلص: Voltage-gated sodium channels (VGSCs) play a key role in the initiation and propagation of action potentials in neurons. NaV1.8 is a tetrodotoxin (TTX) resistant VGSC expressed in nociceptors, peripheral small- diameter neurons able to detect noxious stimuli. NaV1.8 underlies the vast majority of sodium currents during action potentials. Many studies have highlighted a key role for NaV1.8 in inflammatory and chronic pain models. Lipid rafts are microdomains of the plasma membrane highly enriched in cholesterol and sphingolipids. Lipid rafts tune the spatial and temporal organisation of proteins and lipids on the plasma membrane. They are thought to act as platforms on the membrane where proteins and lipids can be trafficked, compartmentalised and functionally clustered. In the present study we investigated NaV1.8 sub-cellular localisation and explored the idea that it is associated with lipid rafts in nociceptors. We found that NaV1.8 is distributed in clusters along the axons of DRG neurons in vitro and ex vivo. We also demonstrated, by biochemical and imaging studies, that NaV1.8 is associated with lipid rafts along the sciatic nerve ex vivo and in DRG neurons in vitro. Moreover, treatments with methyl-β- cyclodextrin (MβCD) and 7-ketocholesterol (7KC) led to the dissociation between rafts and NaV1.8. By calcium imaging we demonstrated that the lack of association between rafts and NaV1.8 correlated with impaired neuronal excitability, highlighted by a reduction in the number of neurons able to conduct mechanically- and chemically-evoked depolarisations. These findings reveal the sub-cellular localisation of NaV1.8 in nociceptors and highlight the importance of the association between NaV1.8 and lipid rafts in the control of nociceptor excitability. [ABSTRACT FROM AUTHOR]

المؤلفون: Ebersberger, Andrea¹ andrea.ebersberger@mti.uni-jena.de, Natura, Gabriel¹, Eitner, Annett², Halbhuber, Karl-Jürgen², Rost, Reinhard¹, Schaible, Hans-Georg¹

المصدر: PAIN. May2011, Vol. 152 Issue 5, p1114-1126. 13p.

مصطلحات موضوعية: *PROSTAGLANDINS, *TETRODOTOXIN, *SODIUM channels, *ANTI-inflammatory agents, *SENSORY neurons, *LABORATORY rats, *NERVOUS system

مستخلص: Abstract: Tetrodotoxin-resistant (TTX-R) Na+ channels play a key role in the generation of action potentials in nociceptive dorsal root ganglion (DRG) neurons and are an important target for the proinflammatory mediator prostaglandin E2, which augments these currents. Prostaglandin D2 (PGD2) is released in the tissue together with prostaglandin E2, and it was reported to be antiinflammatory, but its effect on primary afferent neurons is unclear. In the present study we localised Gs-protein-coupled DP1 and Gi-protein-coupled DP2 receptors in DRG neurons, and we assessed the effect of PGD2 on TTX-R Na+ currents in patch-clamp recordings from small- to medium-sized cultured DRG neurons from adult rats. DP1 and DP2 receptor-like immunoreactivity was localised in the vast majority of DRG neurons. In all neurons, PGD2 shifted conductance to more hyperpolarised potentials, depending on an action at Nav1.9 channels. In about one third of the neurons, PGD2 additionally influenced Nav1.8 channels by facilitating conductance and by increasing maximal current amplitudes. Selective DP1 receptor activation increased the amplitude of TTX-R Na+ currents of most neurons, but this effect was counteracted by DP2 receptor activation, which by itself had no effect. In the current-clamp mode, PGD2 lowered the threshold for elicitation of an action potential and increased the number of action potentials per stimulus, an effect mainly depending on DP1 receptor activation. Thus, the net effect of PGD2 on DRG neurons is pronociceptive, although the magnitude of the TTX-R Na+ currents depends on the balance of DP1 and DP2 receptor activation. Prostaglandin D2 regulates conductance and current amplitudes of tetrodotoxin-resistant sodium channels on dorsal root ganglion neurons by a balanced action at DP1 and DP2 receptor subtypes. [Copyright &y& Elsevier]

المؤلفون: Lin Li¹, Changjin Liu², Lei Chen¹ chenltj@hotmail.com, Ling Chen¹ lingchen@njmu.edu.cn

المصدر: Molecular Pain. 2011, Vol. 7 Issue 1, p27-32. 6p.

مصطلحات موضوعية: *SODIUM channels, *TETRODOTOXIN, *NEURONS, *NEUROTOXIC agents, *NERVOUS system

مستخلص: Voltage-gated sodium channels (VGSCs) play an important role in the control of membrane excitability. We previously reported that the excitability of nociceptor was increased by hypotonic stimulation. The present study tested the effect of hypotonicity on tetrodotoxin-sensitive sodium current (TTX-S current) in cultured trigeminal ganglion (TG) neurons. Our data show that after hypotonic treatment, TTX-S current was increased. In the presence of hypotonicity, voltage-dependent activation curve shifted to the hyperpolarizing direction, while the voltagedependent inactivation curve was not affected. Transient Receptor Potential Vanilloid 4 receptor (TRPV4) activator increased TTX-S current and hypotonicity-induced increase was markedly attenuated by TRPV4 receptor blockers. We also demonstrate that inhibition of PKC attenuated hypotonicity-induced inhibition, whereas PKA system was not involved in hypotonic-response. We conclude that hypotonic stimulation enhances TTX-S current, which contributes to hypotonicity-induced nociception. TRPV4 receptor and PKC intracellular pathway are involved in the increase of TTX-S current by hypotonicity. [ABSTRACT FROM AUTHOR]

المؤلفون: Sultan Al Lawatia, Jerry D. Thomas, Vikas Kapil, Seif Al-Abri, Rebecca M. Coleman, Rudolph C. Johnson, Elizabeth I. Hamelin, Ziad Kazzi, Faryal Khamis, Badria Alhatali, Sandeep Kantur

المصدر: Clinical Toxicology. 60:262-266

مصطلحات موضوعية: Oman, Tetrodotoxin, Pharmacology, Toxicology, Foodborne Diseases, 03 medical and health sciences, chemistry.chemical_compound, Octopus, 0302 clinical medicine, Sodium channel blocker, Tetrodotoxin poisoning, Tandem Mass Spectrometry, biology.animal, medicine, Animals, Humans, 030212 general & internal medicine, biology, musculoskeletal, neural, and ocular physiology, fungi, Neurotoxicity, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Respiratory support, nervous system, chemistry, Toxicity, Acetylcholinesterase, Cholinesterase Inhibitors, Chromatography, Liquid

الوصف: Tetrodotoxin (TTX) is a potent sodium channel blocker, with significant neurotoxicity, found in marine animals like pufferfish and blue-ringed octopus. The severity of toxicity depends on the amount of toxin ingested and the outcome depends on the time-lapse to appropriate medical care.We report five patients who presented with tetrodotoxin poisoning after consuming fried internal organs of local pufferfish from the coast of Oman. The patients' clinical manifestations were consistent with the expected TTX toxidrome of perioral and generalized paresthesia, weakness of upper and lower extremities, gastrointestinal manifestations, dyspnea, dysarthria, ascending paralysis, hypotension, bradycardia and coma. The severity varied among the patients who recovered completely except one patient who developed a subarachnoid hemorrhage without underlying aneurysms on computed tomography-angiogram. This complication was potentially related to TTX poisoning and has not been previously reported. In addition to standard supportive management, patients with severe illness should potentially receive the intravenous acetylcholinesterase inhibitor neostigmine, and intermittent dialysis. Urine specimens were sent to CDC in Atlanta, where they were analyzed using online solid phase extraction (SPE) with LC-MS/MS and confirmed the diagnosis in all five cases.In general, the patients' clinical manifestations were consistent with the expected TTX toxidrome except patient 3 who developed a subarachnoid hemorrhage early during his clinical course. Two patients received neostigmine and underwent dialysis with complete recovery.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25016ede667e36abdd8aac5584cb0b85Test
https://doi.org/10.1080/15563650.2021.1917595Test

المؤلفون: Kiyoshi Kotani, Yasuhiko Jimbo, Kenta Shimba

المصدر: IEEE Transactions on Biomedical Engineering. 68:3574-3581

مصطلحات موضوعية: Neurons, Sodium, Central nervous system, Neural Conduction, Biomedical Engineering, Phrixotoxin, Action Potentials, Tetrodotoxin, Axons, Ion Channels, Rats, chemistry.chemical_compound, medicine.anatomical_structure, nervous system, chemistry, Cerebral cortex, medicine, Neuron maturation, Animals, Channel blocker, Axon, Neuroscience, Ion channel

الوصف: Objective: Neuronal networks are fundamental structures for information processing in the central nervous system. This processing function is severely impaired by abnormal axonal conduction from changes in functional ion channel expression. The evaluation of axonal conduction properties can be effective in the early diagnosis of information-processing abnormalities. However, little is known about functional ion channel expression in axons owing to lack of an appropriate method. In this study, we developed a device to measure changes in axonal conduction properties by selective pharmacological stimulation for the functional evaluation of Na channels expressed in axons. Methods: Axons of rat cortical neurons were guided across a pair of electrodes through microtunnel structures by employing surface patterning. Results: The developed device detected more than 50 axons while recording for 10 min. The conduction delay along the axons decreased by 22.5% with neuron maturation. Tetrodotoxin and lidocaine (Na channel blockers) increased the conduction delay in a concentration-dependent manner depending on their working concentrations, indicating the effectiveness of the device. Finally, selective Na channel blockers for various Na channel subtypes were used. Phrixotoxin, a Nav1.2 blocker, markedly increased the conduction delay, suggesting that Nav1.2 is functionally expressed in the unmyelinated axons of the cerebral cortex. Conclusion: These results show that our device is feasible for the high-throughput functional evaluation of Na channel subtypes in axons. Significance: The results obtained can contribute to the understanding of the pathogenic mechanisms of neurological diseases that involve changes in the functional expression states of ion channels in axons.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::50aff9b1858e2f1cf1858589e837d45aTest
https://doi.org/10.1109/tbme.2021.3078473Test

المؤلفون: Martinov, Vladimir N.¹, Njå, Arild arild.nja@medisin.uio.no

المصدر: Journal of Neuroscience Methods. Feb2005, Vol. 141 Issue 2, p199-205. 7p.

مصطلحات موضوعية: *TETRODOTOXIN, *NEUROTOXIC agents, *NERVOUS system, *ANESTHESIA

مستخلص: Tetrodotoxin (TTX) is a selective blocker of voltage-gated Na+ channels that is used to block action potentials in vitro and in vivo. Maintaining a sufficiently high local concentration of TTX in vivo to block conduction in a peripheral nerve is technically demanding and carries a risk of systemic toxicity. We report that slow diffusion of TTX out of a microcapsule (glass capillary) inserted beneath the epineurium of the sciatic nerve, with a loose cuff around the nerve, combines high blocking efficacy with low systemic toxicity in rats and mice. The local anaesthesia and motor paralysis was stable for at least 4–6 weeks. The conduction block was reversible and did not cause any obvious nerve injury. Low cost and simple surgical implementation make this new system an interesting alternative to existing long-term drug delivery methods. [Copyright &y& Elsevier]

المؤلفون: Bahar Tokur, Koray Korkmaz

المصدر: Natural and Engineering Sciences, Vol 6, Iss 1, Pp 39-52 (2021)
Volume: 6, Issue: 1 39-52
Natural and Engineering Sciences

مصطلحات موضوعية: pufferfish,tetrodotoxin (TTX),TTX-binding protein, Chemistry, musculoskeletal, neural, and ocular physiology, fungi, Mühendislik, Zoology, Engineering, nervous system, ttx-binding protein, Tetrodotoxin-binding protein, pufferfish, lcsh:TA1-2040, Fish , heterocyclic compounds, tetrodotoxin (ttx), lcsh:Engineering (General). Civil engineering (General), lcsh:Science (General), lcsh:Q1-390

الوصف: Marine pufferfish generally involve a potent neurotoxin, tetrodotoxin (TTX), which might be the leading cause for many human intoxications. It blocks nervous impulses’ conduction along nerve fibers and axons during the act, and the LD50 for the mouse is 10 nanograms. Being much larger than the sodium ion, TTX acts as a cork of a bottle, prevents sodium from flowing until it diffuses slowly. The TTX expanse appears to be species-specific in pufferfish bodies. The toxin is thought to bioaccumulate via the marine food based on the observations that marine pufferfishes that are cultured are not toxic, and non-toxic cultured pufferfishes become toxic when they feed on TTX-containing artificial diets. TTX-bearing animals show incredibly high resistance to TTX, and therefore TTX presumably retains or accumulates as a biological defense substance. These animals carrying TTX can accumulate toxins in their bodies despite not killing themselves is an object of interest. Fort his reason, and it is argued that TTX is wrapped in a particular protein and does not bind directly to the target's side-sodium channel, and therefore does not induce intoxication. The pufferfish TTX-binding protein (PSTBP) was first isolated as a potential TTX-carrier protein from the plasma of the marine pufferfish Takifugu niphobles. This protein is discovered to be a dimeric glycoprotein and formed a non-covalent dimer.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e670443e81bc5253b6339e1465d0ae78Test
https://www.nesciences.com/download.php?id=626Test

المؤلفون: Valery P. Zinchenko, Artem M. Kosenkov, Sergei A. Maiorov, S. G. Gaidin

المصدر: Neuroscience Research. 171:27-33

مصطلحات موضوعية: 0301 basic medicine, Agonist, medicine.drug_class, Population, Kainate receptor, Hippocampal formation, Synaptic Transmission, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Receptors, Kainic Acid, medicine, education, Receptor, gamma-Aminobutyric Acid, Neurons, education.field_of_study, Chemistry, General Neuroscience, Depolarization, General Medicine, 030104 developmental biology, nervous system, Synapses, Tetrodotoxin, GABAergic, Neuroscience, 030217 neurology & neurosurgery

الوصف: Hippocampal GABAergic neurons are subdivided into more than 20 subtypes that are distinguished by features and functions. We have previously described the subpopulation of GABAergic neurons, which can be identified in hippocampal cell culture by the calcium response to the application of domoic acid (DoA), an agonist of kainate receptors (KARs). Here, we investigate the features of DoA-sensitive neurons and their GABA release mechanism in response to KARs activation. We demonstrate that DoA-sensitive GABAergic neurons express GluK1-containing KARs because ATPA, a selective agonist of GluK1-containing receptors, induces the calcium response exclusively in these GABAergic neurons. Our experiments also show that NASPM, previously considered a selective antagonist of calcium-permeable AMPARs, blocks calcium-permeable KARs. We established using NASPM that GluK1-containing receptors of the studied population of GABAergic neurons are calcium-permeable, and their activation is required for GABA release, at least in particular synapses. Notably, GABA release occurs even in the presence of tetrodotoxin, indicating that propagation of the depolarizing stimulus is not required for GABA release in this case. Thus, our data demonstrate that the activation of GluK1-containing calcium-permeable KARs mediates the GABA release by the studied subpopulation of GABAergic neurons.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a34422c8f2643d4d111c6992abf55a9fTest
https://doi.org/10.1016/j.neures.2021.03.009Test

المؤلفون: Mònica Campàs, Panagiota Katikou, Ali Rıza Kosker, Fatih OZOGUL, Cengiz Gokbulut

المساهمون: Producció Animal, Aigües Marines i Continentals

المصدر: IRTA Pubpro. Open Digital Archive
Institut de Recerca i Tecnologia Agroalimentàries (IRTA)
Marine Drugs
Marine Drugs, Vol 20, Iss 47, p 47 (2022)

مصطلحات موضوعية: China, QH301-705.5, Pharmaceutical Science, Review, tetrodotoxin (TTX), Tetrodotoxin, edible marine organisms, Japan, Drug Discovery, Mediterranean Sea, Animals, Humans, heterocyclic compounds, Biology (General), Indian Ocean, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Tetraodontiformes, Incidence, musculoskeletal, neural, and ocular physiology, public health, Ciguatera Poisoning, Thailand, nervous system, pufferfish, marine toxins

الوصف: Tetrodotoxin (TTX) is a crystalline, weakly basic, colorless organic substance and is one of the most potent marine toxins known. Although TTX was first isolated from pufferfish, it has been found in numerous other marine organisms and a few terrestrial species. Moreover, tetrodotoxication is still an important health problem today, as TTX has no known antidote. TTX poisonings were most commonly reported from Japan, Thailand, and China, but today the risk of TTX poisoning is spreading around the world. Recent studies have shown that TTX-containing fish are being found in other regions of the Pacific and in the Indian Ocean, as well as the Mediterranean Sea. This review aims to summarize pertinent information available to date on the structure, origin, distribution, mechanism of action of TTX and analytical methods used for the detection of TTX, as well as on TTX-containing organisms, symptoms of TTX poisoning, and incidence worldwide. info:eu-repo/semantics/publishedVersion

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b12c50f18196589f25f9c5af724f434Test
http://hdl.handle.net/20.500.12327/1614Test