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https://www.readbyqxmd.com/read/28338073/veratridine-produces-distinct-calcium-response-profiles-in-mouse-dorsal-root-ganglia-neurons
#1
Zainab A Mohammed, Ciara Doran, David Grundy, Mohammed A Nassar
Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an "agonist" in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238546/regulation-of-thalamic-and-cortical-network-synchrony-by-scn8a
#2
Christopher D Makinson, Brian S Tanaka, Jordan M Sorokin, Jennifer C Wong, Catherine A Christian, Alan L Goldin, Andrew Escayg, John R Huguenard
Voltage-gated sodium channel (VGSC) mutations cause severe epilepsies marked by intermittent, pathological hypersynchronous brain states. Here we present two mechanisms that help to explain how mutations in one VGSC gene, Scn8a, contribute to two distinct seizure phenotypes: (1) hypoexcitation of cortical circuits leading to convulsive seizure resistance, and (2) hyperexcitation of thalamocortical circuits leading to non-convulsive absence epilepsy. We found that loss of Scn8a leads to altered RT cell intrinsic excitability and a failure in recurrent RT synaptic inhibition...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28124609/recombinant-expression-functional-characterization-of-two-scorpion-venom-toxins-with-three-disulfide-bridges-from-the-chinese-scorpion-buthus-martensii-karsch
#3
ShengGuo Lin, XueLin Wang, XueYao Hu, YongShan Zhao, MingYi Zhao, JingHai Zhang, Yong Cui
Scorpion venom contains a large variety of biologically active peptides. However, most of these peptides have not been identified and characterized. Peptides with three disulfide bridges, existing in the scorpion venom, have not been studied in detail and have been poorly characterized until now. Here, we report the recombinant expression and functional characterization of two kinds of venom peptides (BmKBTx and BmNaL-3SS2) with three disulfide bridges. This study adopted an effective E. coli system. The genes for BmKBTx and BmNaL-3SS2 were obtained by the Polymerase Chain Reaction method and finally cloned to the pSYPU-1b vector...
January 17, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28118359/the-ampk-activator-a769662-blocks-voltage-gated-sodium-channels-discovery-of-a-novel-pharmacophore-with-potential-utility-for-analgesic-development
#4
Marina N Asiedu, Chongyang Han, Sulayman D Dib-Hajj, Stephen G Waxman, Theodore J Price, Gregory Dussor
Voltage-gated sodium channels (VGSC) regulate neuronal excitability by governing action potential (AP) generation and propagation. Recent studies have revealed that AMP-activated protein kinase (AMPK) activators decrease sensory neuron excitability, potentially by preventing sodium (Na+) channel phosphorylation by kinases such as ERK or via modulation of translation regulation pathways. The direct positive allosteric modulator A769662 displays substantially greater efficacy than other AMPK activators in decreasing sensory neuron excitability suggesting additional mechanisms of action...
2017: PloS One
https://www.readbyqxmd.com/read/28078312/biallelic-scn10a-mutations-in-neuromuscular-disease-and-epileptic-encephalopathy
#5
Marios Kambouris, Julien Thevenon, Ariane Soldatos, Allison Cox, Joshi Stephen, Tawfeg Ben-Omran, Yasser Al-Sarraj, Hala Boulos, William Bone, James C Mullikin, Alice Masurel-Paulet, Judith St-Onge, Yannis Dufford, Corrine Chantegret, Christel Thauvin-Robinet, Jamil Al-Alami, Laurence Faivre, Jean Baptiste Riviere, William A Gahl, Alexander G Bassuk, May Christine V Malicdan, Hatem El-Shanti
OBJECTIVES: Two consanguineous families, one of Sudanese ethnicity presenting progressive neuromuscular disease, severe cognitive impairment, muscle weakness, upper motor neuron lesion, anhydrosis, facial dysmorphism, and recurrent seizures and the other of Egyptian ethnicity presenting with neonatal hypotonia, bradycardia, and recurrent seizures, were evaluated for the causative gene mutation. METHODS AND RESULTS: Homozygosity mapping and whole exome sequencing (WES) identified damaging homozygous variants in SCN10A, namely c...
January 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27994149/fgf14-is-a-regulator-of-kcnq2-3-channels
#6
Juan Lorenzo Pablo, Geoffrey S Pitt
KCNQ2/3 (Kv7.2/7.3) channels and voltage-gated sodium channels (VGSCs) are enriched in the axon initial segment (AIS) where they bind to ankyrin-G and coregulate membrane potential in central nervous system neurons. The molecular mechanisms supporting coordinated regulation of KCNQ and VGSCs and the cellular mechanisms governing KCNQ trafficking to the AIS are incompletely understood. Here, we show that fibroblast growth factor 14 (FGF14), previously described as a VGSC regulator, also affects KCNQ function and localization...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27867092/peptide-rich-venom-from-the-spider-heteropoda-venatoria-potently-inhibits-insect-voltage-gated-sodium-channels
#7
Yazhou Huang, Xinzhou Wu, Peng Zhang, Zhigui Duan, Xi Zhou, Minzhi Chen, Athar Farooq, Songping Liang, Zhonghua Liu
Heteropoda venatoria is a venomous spider species distributed worldwide and has a characteristic habit of feeding on insects. Reverse-phase high-performance liquid chromatography and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry analyses revealed that H. venatoria venom contains hundreds of peptides with a predominant molecular weights of 3000-5000 Da. Intra-abdominal injection of the venom had severe toxic effects on cockroaches and caused death at higher concentrations. The LD50 was 28...
January 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27819327/structure-and-function-of-fs50-a-salivary-protein-from-the-flea-xenopsylla-cheopis-that-blocks-the-sodium-channel-nav1-5
#8
Xueqing Xu, Bei Zhang, Shilong Yang, Su An, José M C Ribeiro, John F Andersen
Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 μM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815510/voltage-gated-sodium-channels-and-pain-related-disorders
#9
REVIEW
Alexandros H Kanellopoulos, Ayako Matsuyama
Voltage-gated sodium channels (VGSCs) are heteromeric transmembrane protein complexes. Nine homologous members, SCN1A-11A, make up the VGSC gene family. Sodium channel isoforms display a wide range of kinetic properties endowing different neuronal types with distinctly varied firing properties. Among the VGSCs isoforms, Nav1.7, Nav1.8 and Nav1.9 are preferentially expressed in the peripheral nervous system. These isoforms are known to be crucial in the conduction of nociceptive stimuli with mutations in these channels thought to be the underlying cause of a variety of heritable pain disorders...
December 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27799911/huperzine-a-provides-robust-and-sustained-protection-against-induced-seizures-in-scn1a-mutant-mice
#10
Jennifer C Wong, Stacey B B Dutton, Stephen D Collins, Steven Schachter, Andrew Escayg
De novo loss-of-function mutations in the voltage-gated sodium channel (VGSC) SCN1A (encoding Nav1.1) are the main cause of Dravet syndrome (DS), a catastrophic early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), refractory afebrile epilepsy, cognitive and behavioral deficits, and a 15-20% mortality rate. SCN1A mutations also lead to genetic epilepsy with febrile seizures plus (GEFS+), which is an inherited disorder characterized by early-life FSs and the development of a range of adult epilepsy subtypes...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27752065/engineering-prokaryotic-channels-for-control-of-mammalian-tissue-excitability
#11
Hung X Nguyen, Robert D Kirkton, Nenad Bursac
The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes...
October 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27723825/multiple-insecticide-resistance-in-the-malaria-vector-anopheles-funestus-from-northern-cameroon-is-mediated-by-metabolic-resistance-alongside-potential-target-site-insensitivity-mutations
#12
Benjamin D Menze, Jacob M Riveron, Sulaiman S Ibrahim, Helen Irving, Christophe Antonio-Nkondjio, Parfait H Awono-Ambene, Charles S Wondji
BACKGROUND: Despite the recent progress in establishing the patterns of insecticide resistance in the major malaria vector Anopheles funestus, Central African populations of this species remain largely uncharacterised. To bridge this important gap and facilitate the implementation of suitable control strategies against this vector, we characterised the resistance patterns of An. funestus population from northern Cameroon. METHODS AND FINDINGS: Collection of indoor-resting female mosquitoes in Gounougou (northern Cameroon) in 2012 and 2015 revealed a predominance of An...
2016: PloS One
https://www.readbyqxmd.com/read/27703972/corrigendum-to-vgsc-a-web-based-vector-graph-toolkit-of-genome-synteny-and-collinearity
#13
Yiqing Xu, Changwei Bi, Guoxin Wu, Suyun Wei, Xiaogang Dai, Tongming Yin, Ning Ye
[This corrects the article DOI: 10.1155/2016/7823429.].
2016: BioMed Research International
https://www.readbyqxmd.com/read/27697698/characterization-of-brevetoxin-pbtx-3-exposure-in-neurons-of-the-anoxia-tolerant-freshwater-turtle-trachemys-scripta
#14
Courtney C Cocilova, Sarah L Milton
Harmful algal blooms are increasing in frequency and extent worldwide and occur nearly annually off the west coast of Florida where they affect both humans and wildlife. The dinoflagellate Karenia brevis is a key organism in Florida red tides that produces a suite of potent neurotoxins collectively referred to as the brevetoxins (PbTx). Brevetoxins bind to and open voltage gated sodium channels (VGSC), increasing cell permeability in excitable cells and depolarizing nerve and muscle tissue. Exposed animals may thus show muscular and neurological symptoms including head bobbing, muscle twitching, paralysis, and coma; large HABs can result in significant morbidity and mortality of marine life, including fish, birds, marine mammals, and sea turtles...
November 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27601493/sodium-channel-inhibiting-drugs-and-cancer-survival-protocol-for-a-cohort-study-using-the-cprd-primary-care-database
#15
Caroline Fairhurst, Fabiola Martin, Ian Watt, Tim Doran, Martin Bland, William J Brackenbury
INTRODUCTION: Voltage-gated sodium channel (VGSC)-inhibiting drugs are commonly used to treat epilepsy and cardiac arrhythmia. VGSCs are also widely expressed in various cancers, including those of the breast, bowel and prostate. A number of VGSC-inhibiting drugs have been shown to inhibit cancer cell proliferation, invasion, tumour growth and metastasis in preclinical models, suggesting that VGSCs may be novel molecular targets for cancer treatment. Surprisingly, we previously found that prior exposure to VGSC-inhibiting drugs may be associated with reduced overall survival in patients with cancer, but we were unable to control for the cause of death or indication for prescription...
September 6, 2016: BMJ Open
https://www.readbyqxmd.com/read/27597416/new-arylalkyl-azole-derivatives-showing-anticonvulsant-effects-could-have-vgsc-and-or-gabaar-affinity-according-to-molecular-modeling-studies
#16
Suat Sari, Arzu Karakurt, Harun Uslu, F Betül Kaynak, Ünsal Çalış, Sevim Dalkara
(Arylalkyl)azoles (AAAs) emerged as a novel class of antiepileptic agents with the invention of nafimidone and denzimol. Several AAA derivatives with potent anticonvulsant activities have been reported so far, however neurotoxicity was usually an issue. We prepared a set of ester derivatives of 1-(2-naphthyl)-2-(1H-1,2,4-triazol-1-yl)ethanone oxime and evaluated their anticonvulsant and neurotoxic effects in mice. Most of our compounds were protective against maximal electroshock (MES)- and/or subcutaneous metrazol (s...
November 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27586289/developmental-and-regulatory-functions-of-na-channel-non-pore-forming-%C3%AE-subunits
#17
J J Winters, L L Isom
Voltage-gated Na(+) channels (VGSCs) isolated from mammalian neurons are heterotrimeric complexes containing one pore-forming α subunit and two non-pore-forming β subunits. In excitable cells, VGSCs are responsible for the initiation of action potentials. VGSC β subunits are type I topology glycoproteins, containing an extracellular amino-terminal immunoglobulin (Ig) domain with homology to many neural cell adhesion molecules (CAMs), a single transmembrane segment, and an intracellular carboxyl-terminal domain...
2016: Current Topics in Membranes
https://www.readbyqxmd.com/read/27586281/venom-peptides-from-cone-snails-pharmacological-probes-for-voltage-gated-sodium-channels
#18
B R Green, B M Olivera
The venoms of cone snails provide a rich source of neuroactive peptides (conotoxins). Several venom peptide families have been identified that are either agonists (ι- and δ-conotoxins) or antagonists (μ- and μO-conotoxins) of voltage-gated sodium channels (VGSCs). Members of these conotoxin classes have been integral in identifying and characterizing specific neurotoxin binding sites on the channel. Furthermore, given the specificity of some of these peptides for one sodium channel subtype over another, conotoxins have also proven useful in exploring differences between VGSC subtypes...
2016: Current Topics in Membranes
https://www.readbyqxmd.com/read/27529686/voltage-gated-sodium-channel-nav-1-7-promotes-gastric-cancer-progression-through-macc1-mediated-upregulation-of-nhe1
#19
Jianling Xia, Na Huang, Hongxiang Huang, Li Sun, Shaoting Dong, Jinyu Su, Jingwen Zhang, Lin Wang, Li Lin, Min Shi, Jianping Bin, Yulin Liao, Nailin Li, Wangjun Liao
Voltage-gated sodium channels (VGSCs), which are aberrantly expressed in several human cancers, affect cancer cell behavior; however, their role in gastric cancer (GC) and the link between these channels and tumorigenic signaling remain unclear. The aims of this study were to determine the clinicopathological significance and role of the VGSC Nav 1.7 in GC progression and to investigate the associated mechanisms. Here, we report that the SCN9A gene encoding Nav 1.7 was the most abundantly expressed VGSC subtype in GC tissue samples and two GC cell lines (BGC-823 and MKN-28 cells)...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27527509/diversity-and-frequency-of-kdr-mutations-within-anopheles-sinensis-populations-from-guangxi-china
#20
Chan Yang, Xiangyang Feng, Zushi Huang, Mei Li, Xinghui Qiu
BACKGROUND: Anopheles sinensis is a major vector of malaria in China and its control is under great threat as the development of insecticide resistance. Voltage-gated sodium channel (VGSC) is the target of several classes of insecticides. Genetic mutations of VGSC have been documented to confer knockdown resistance (kdr) to dichlorodiphenyltrichloroethane (DDT) and pyrethroids in mosquitoes. To control this vector efficiently, it is important to know the resistance-associated genetic mutations, their distribution frequencies and genealogical relations...
2016: Malaria Journal
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