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Voltage-gated sodium channel

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https://www.readbyqxmd.com/read/29161016/selective-voltage-gated-sodium-channel-peptide-toxins-from-animal-venom-pharmacological-probes-and-analgesic-drug-development
#1
Ying Wu, Hui Ma, Fan Zhang, Chun-Lei Zhang, Xiaohan Zou, Zhengyu Cao
Voltage-gated sodium channels (Navs) play critical roles in action potential generation and propagation. Nav channelopathy as well as pathological sensitization contribute to allodynia and hyperalgesia. Recent evidence has demonstrated the significant roles of Nav subtypes (Nav1.3, 1.7, 1.8 and 1.9) in nociceptive transduction and therefore these Navs may represent attractive targets for analgesic drug discovery. Animal toxins are structurally diverse peptides that are highly potent yet selective on ion channel subtypes and therefore representing valuable probes to elucidate the structures, gating properties and cellular functions of ion channels...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29158847/photoactive-poly-3-hexylthiophene-nanoweb-for-optoelectrical-stimulation-to-enhance-neurogenesis-of-human-stem-cells
#2
Kisuk Yang, Jin Young Oh, Jong Seung Lee, Yoonhee Jin, Gyeong-Eon Chang, Soo Sang Chae, Eunji Cheong, Hong Koo Baik, Seung-Woo Cho
Optoelectrical manipulation has recently gained attention for cellular engineering; however, few material platforms can be used to efficiently regulate stem cell behaviors via optoelectrical stimulation. In this study, we developed nanoweb substrates composed of photoactive polymer poly(3-hexylthiophene) (P3HT) to enhance the neurogenesis of human fetal neural stem cells (hfNSCs) through photo-induced electrical stimulation. METHODS: The photoactive nanoweb substrates were fabricated by self-assembled one-dimensional (1D) P3HT nanostructures (nanofibrils and nanorods)...
2017: Theranostics
https://www.readbyqxmd.com/read/29158414/molecular-basis-of-selective-resistance-of-the-bumblebee-binav1-sodium-channel-to-tau-fluvalinate
#3
Shaoying Wu, Yoshiko Nomura, Yuzhe Du, Boris S Zhorov, Ke Dong
Insecticides are widely used to control pests in agriculture and insect vectors that transmit human diseases. However, these chemicals can have a negative effect on nontarget, beneficial organisms including bees. Discovery and deployment of selective insecticides is a major mission of modern toxicology and pest management. Pyrethroids exert their toxic action by acting on insect voltage-gated sodium channels. Honeybees and bumblebees are highly sensitive to most pyrethroids, but are resistant to a particular pyrethroid, tau-fluvalinate (τ-FVL)...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29155487/novel-cyp6d1-and-voltage-gated-sodium-channel-alleles-of-the-house-fly-musca-domestica-and-their-roles-in-pyrethroid-resistance
#4
Jing Pan, Chan Yang, Yan Liu, Qi Gao, Mei Li, Xinghui Qiu
BACKGROUND: The house fly Musca domestica is an important disease vector. Point mutation mediated target-site insensitivity of the voltage gated sodium channel (VSSC) and increased detoxification mediated by CYP6D1 overexpression have been characterized to be two major mechanisms of pyrethroid resistance. In this study, genetic mutations in Vssc and CYP6D1 genes and their contribution to pyrethroid resistance were investigated. RESULTS: Twelve lines of house flies homozygous for four genotypes were established...
November 20, 2017: Pest Management Science
https://www.readbyqxmd.com/read/29146176/neosaxitoxin-a-paralytic-shellfish-poison-toxin-effectively-manages-bucked-shins-pain-as-a-local-long-acting-pain-blocker-in-an-equine-model
#5
Gricel Riquelme, Joaquín M Sepúlveda, Zaki Al Ghumgham, Miguel Del Campo, Cecilia Montero, Nestor Lagos
Local anesthesia is an effective method to control pain. Neosaxitoxin is a phycotoxin whose molecular mechanism includes a reversible inhibition of voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. The present study was designed to evaluate the clinical efficacy of Neosaxitoxin as a local long-acting pain blocker in horse bucked shins, and it was found to effectively control pain. While Neosaxitoxin and Gonyautoxin, another Paralytic Shellfish Poison (PSP) toxin, have been successfully used in humans as long-lasting pain blockers, this finding marks the first time a PSP has been shown to have an established effect in veterinary medicine...
November 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29145747/two-novel-families-with-hemiplegic-migraine-caused-by-recurrent-scn1a-mutation-p-f1499l
#6
Victoria Schubert, Eva Auffenberg, Saskia Biskup, Karin Jurkat-Rott, Tobias Freilinger
Background Familial hemiplegic migraine type 3 is a monogenic subtype of migraine caused by missense mutations in the neuronal voltage-gated sodium channel gene SCN1A, with 10 different mutations reported so far. In two familial hemiplegic migraine type 3 families, partial cosegregation with a rare eye phenotype (elicited repetitive daily blindness) was previously reported. Methods Two novel familial hemiplegic migraine pedigrees were subjected to genetic analysis and detailed work-up of associated clinical features...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29142310/sodium-channel-nav1-3-is-important-for-enterochromaffin-cell-excitability-and-serotonin-release
#7
Peter R Strege, Kaitlyn Knutson, Samuel J Eggers, Joyce H Li, Fan Wang, David Linden, Joseph H Szurszewski, Lorin Milescu, Andrew B Leiter, Gianrico Farrugia, Arthur Beyder
In the gastrointestinal (GI) epithelium, enterochromaffin (EC) cells are enteroendocrine cells responsible for producing >90% of the body's serotonin (5-hydroxytryptamine, 5-HT). However, the molecular mechanisms of EC cell function are poorly understood. Here, we found that EC cells in mouse primary cultures fired spontaneous bursts of action potentials. We examined the repertoire of voltage-gated sodium channels (NaV) in fluorescence-sorted mouse EC cells and found that Scn3a was highly expressed. Scn3a-encoded NaV1...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138928/mechanisms-of-drug-binding-to-voltage-gated-sodium-channels
#8
M E O'Leary, M Chahine
Voltage-gated sodium (Na(+)) channels are expressed in virtually all electrically excitable tissues and are essential for muscle contraction and the conduction of impulses within the peripheral and central nervous systems. Genetic disorders that disrupt the function of these channels produce an array of Na(+) channelopathies resulting in neuronal impairment, chronic pain, neuromuscular pathologies, and cardiac arrhythmias. Because of their importance to the conduction of electrical signals, Na(+) channels are the target of a wide variety of local anesthetic, antiarrhythmic, anticonvulsant, and antidepressant drugs...
November 15, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29138838/effects-of-scn9a-gene-modification-on-na-channel-and-the-expression-of-nerve-growth-factor-in-a-rat-model-of-diarrhea%C3%A2-predominant-irritable-bowel-syndrome
#9
Yong-Yan Cai, Chen Li, Zhi-Xin Yan, Na Ma, Fang-Fang Li
The aim of the present study was to identify whether the sodium voltage-gated channel alpha subunit 9 (SCN9A) gene modification is a potential treatment for diarrhea‑predominant irritable bowel syndrome (D‑IBS), via regulating the Na+ channel and the expression of nerve growth factor (NGF). The recombinant adenovirus vector of the SCN9A gene was established, and rat colon cells were isolated for SCN9A gene modification. All subjects were divided into four groups: i) The SCN9A‑modified (D‑IBS rat model implanted with SCN9A‑modified colon cells), ii) negative control (NC; D‑IBS rat model implanted with colon cells without SCN9A gene modification), iii) blank (D‑IBS rat model without any treatment) and iv) normal (normal rats without any treatment)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29128679/early-onset-epileptic-encephalopathy-with-de-novo-scn8a-mutation
#10
Yangyang Xiao, Jie Xiong, Ding'an Mao, Lingjuan Liu, Jian Li, Xingfang Li, Haiyan Luo, Liqun Liu
Early-onset epileptic encephalopathies (EOEEs) are clinically and genetically heterogeneous disorders characterized by intractable seizures and unremitting interictal paroxysmal epileptiform activity. Consequently, these syndromes impair neurodevelopment during the first year of life. Currently, the etiology of these disorders is largely unknown. In this study, Childhood-Onset Epilepsy Gene Panel Testing (containing 511 epilepsy-related genes) was performed in a parent-offspring trio. In this family, the son had refractory seizures, intellectual disability, and motor abnormalities, and he was diagnosed with EOEE...
October 28, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29122010/expression-of-voltage-gated-sodium-channel-nav1-5-in-non-metastatic-colon-cancer-and-its-associations-with-estrogen-receptor-er-%C3%AE-expression-and-clinical-outcomes
#11
Jianhong Peng, Qingjian Ou, Xiaojun Wu, Rongxin Zhang, Qian Zhao, Wu Jiang, Zhenhai Lu, Desen Wan, Zhizhong Pan, Yujing Fang
BACKGROUND: Voltage-gated sodium channel 1.5 (Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β (ER-β) expression in non-metastatic colon cancer patients receiving radical resection. METHODS: A total of 269 consecutive patients with pathologically confirmed stages I-III colon cancer who underwent radical resection were selected...
November 9, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/29119925/post-treatment-with-a-hydrogen-sulfide-donor-limits-neuronal-injury-and-modulates-potassium-voltage-gated-channel-subfamily-d-member-2-kv4-2-and-potassium-channel-interacting-protein-3-kchip3-during-transient-global-cerebral-ischemia
#12
Cheng-Ping Bai, ChenLiang Zhao, Lijuan Shen
BACKGROUND: Although the neuroprotective effect of sodium hydrosulfide (NaHS, a hydrogen sulfide donor) pretreatment has been revealed, the effect of NaHS post-conditioning remains largely unknown. OBJECTIVE: We aimed to investigate the neuroprotective effect of NaHS post-conditioning against transient global cerebral ischemia (tGCI)-induced hippocampal CA1 injury and its underlying molecular mechanism. METHODS: A tGCI rat model was established using the four-vessel occlusion method for 15 min of ischemia...
November 7, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29115566/downregulation-of-microrna%C3%A2-155-by-preoperative-administration-of-valproic-acid-prevents-postoperative-seizures-by-upregulating-scn1a
#13
Zhijie Zhang, Zhenzhong Wang, Bo Zhang, Yan Liu
The risk of seizure is increased following brain surgery such as cranioplasty. Patients with seizures that are treated with valproic acid (VPA) may have a decreased risk of further seizures. To verify microRNA (miR)‑155 as a potential biomarker for the occurrence of seizures, reverse transcription quantitative polymerase chain reaction (RT‑qPCR) was used. Computational analysis and luciferase reporter assay was performed to identify the putative target of miR‑155. RT‑qPCR and western blot analyses were used to determine the expression level of miR‑155, sodium voltage‑gated channel α subunit 1 (SCN1A) mRNA and protein...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29106681/common-missense-variant-of-scn9a-gene-is-associated-with-pain-intensity-in-patients-with-chronic-pain-from-disc-herniation
#14
Mateusz Kurzawski, Marcin Rut, Violetta Dziedziejko, Krzysztof Safranow, Anna Machoy-Mokrzynska, Marek Drozdzik, Monika Bialecka
Objective: Lumbar intervertebral disk herniation (LDH) is considered one of the major risk factors for lower back pain, mainly caused by irritation of a spinal nerve or its root. One of the genes related to pain perception is SCN9A, which encodes the voltage gated sodium channel NaV1.7, a key molecule involved in peripheral pain processing. It had been presented before that a common polymorphism within SCN9A (rs6746030: G > A, R1150W) might influence nociception in the general population...
November 2, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29103950/genotyping-acaricide-resistance-profiles-of-rhipicephalus-microplus-tick-populations-from-communal-land-areas-of-zimbabwe
#15
Marvelous Sungirai, Samantha Baron, Doreen Zandile Moyo, Patrick De Clercq, Christine Maritz-Olivier, Maxime Madder
Acaricide resistance is one of the greatest threats towards the successful control of vector ticks worldwide. Communal farmers of Zimbabwe use amitraz as the most common acaricide with occasional usage of pyrethroids and organophosphates. As a strategy towards developing an effective acaricide resistance management system in Zimbabwe, screening was done by genotyping Rhipicephalus microplus tick populations using molecular markers associated with resistance to these chemicals. The frequency of the mutant allele for the octopamine/tyramine receptor marker associated with amitraz resistance was high (0...
November 2, 2017: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/29094210/evolutionary-history-of-voltage-gated-sodium-channels
#16
Atsuo Nishino, Yasushi Okamura
Every cell within living organisms actively maintains an intracellular Na(+) concentration that is 10-12 times lower than the extracellular concentration. The cells then utilize this transmembrane Na(+) concentration gradient as a driving force to produce electrical signals, sometimes in the form of action potentials. The protein family comprising voltage-gated sodium channels (NaVs) is essential for such signaling and enables cells to change their status in a regenerative manner and to rapidly communicate with one another...
November 2, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29089585/antibodies-against-peripheral-nerve-antigens-in-chronic-inflammatory-demyelinating-polyradiculoneuropathy
#17
Luis Querol, Ana M Siles, Roser Alba-Rovira, Agustín Jáuregui, Jérôme Devaux, Catherine Faivre-Sarrailh, Josefa Araque, Ricard Rojas-Garcia, Jordi Diaz-Manera, Elena Cortés-Vicente, Gisela Nogales-Gadea, Miquel Navas-Madroñal, Eduard Gallardo, Isabel Illa
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous disease in which diverse autoantibodies have been described but systematic screening has never been performed. Detection of CIDP-specific antibodies may be clinically useful. We developed a screening protocol to uncover novel reactivities in CIDP. Sixty-five CIDP patients and 28 controls were included in our study. Three patients (4.6%) had antibodies against neurofascin 155, four (6.2%) against contactin-1 and one (1.5%) against the contactin-1/contactin-associated protein-1 complex...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29081751/new-theoretical-model-of-nerve-conduction-in-unmyelinated-nerves
#18
Tetsuya Akaishi
Nerve conduction in unmyelinated fibers has long been described based on the equivalent circuit model and cable theory. However, without the change in ionic concentration gradient across the membrane, there would be no generation or propagation of the action potential. Based on this concept, we employ a new conductive model focusing on the distribution of voltage-gated sodium ion channels and Coulomb force between electrolytes. Based on this new model, the propagation of the nerve conduction was suggested to take place far before the generation of action potential at each channel...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29079902/structural-models-of-ligand-bound-sodium-channels
#19
Boris S Zhorov
X-ray and cryo-EM structures of tetrameric and pseudo-tetrameric P-loop channels are used to elaborate homology models of mammalian voltage-gated sodium channels with drugs and neurotoxins. Such models integrate experimental data, assist in planning new experiments, and may facilitate drug design. This chapter outlines sodium channel models with local anesthetics, anticonvulsants, and antiarrhythmics, which are used to manage pain and treat sodium channelopathies. Further summarized are sodium channel models with tetrodotoxin, mu-conotoxins, batrachotoxin, scorpion toxins, and insecticides...
September 14, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29079725/complementary-mechanisms-for-neurotoxin-resistance-in-a-copepod
#20
Vittoria Roncalli, Petra H Lenz, Matthew C Cieslak, Daniel K Hartline
Toxin resistance is a recurring evolutionary response by predators feeding on toxic prey. These adaptations impact physiological interaction and community ecology. Mechanisms for resistance vary depending on the predator and the nature of the toxin. Potent neurotoxins like tetrodotoxin (TTX) and saxitoxin (STX) that are highly toxic to humans and other vertebrates, target conserved voltage-gated sodium channels (NaV) of nerve and muscle, causing paralysis. The copepod Calanus finmarchicus consumes the STX-producing dinoflagellate, Alexandrium fundyense with no effect on survival...
October 27, 2017: Scientific Reports
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