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https://www.readbyqxmd.com/read/27867092/peptide-rich-venom-from-the-spider-heteropoda-venatoria-potently-inhibits-insect-voltage-gated-sodium-channels
#1
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...
November 17, 2016: 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
September 28, 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
#9
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...
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
#10
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...
August 25, 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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27493252/knockdown-resistance-mutations-in-aedes-aegypti-diptera-culicidae-from-puerto-rico
#15
Gustavo Ponce-García, Samantha Del Río-Galvan, Roberto Barrera, Karla Saavedra-Rodriguez, Karina Villanueva-Segura, Gilberto Felix, Manuel Amador, Adriana E Flores
Permethrin resistance is widespread in Aedes aegypti (L.), the main dengue, zika, and chikungunya virus vector in Latin America and the Caribbean. A common mechanism of resistance to pyrethroids-knockdown resistance (kdr)-is conferred through mutations in the insect's voltage-dependent sodium channel. In this mosquito, around 10 replacement substitutions in the voltage-gated sodium channel gene (vgsc) have been reported in pyrethroid-resistant strains. Two of these mutations, named Ile1,016 and Cys1,534, are widespread in mosquito populations from Latin America and the Caribbean...
November 2016: Journal of Medical Entomology
https://www.readbyqxmd.com/read/27439594/expression-patterns-mutation-detection-and-rna-interference-of-rhopalosiphum-padi-voltage-gated-sodium-channel-genes
#16
Yayun Zuo, Xiong Peng, Kang Wang, Fangfei Lin, Yuting Li, Maohua Chen
The voltage-gated sodium channel (VGSC) is the target of sodium-channel-blocking insecticides. Traditionally, animals were thought to have only one VGSC gene comprising a α-subunit with four homologous domains (DI-DIV). The present study showed that Rhopalosiphum padi, an economically important crop pest, owned a unique heterodimeric VGSC (H1 and H2 subunits) encoded by two genes (Rpvgsc1 and Rpvgsc2), which is unusual in insects and other animals. The open reading frame (ORF) of Rpvgsc1 consisted 1150 amino acids, and the ORF of Rpvgsc2 had 957 amino acids...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27416771/larval-application-of-sodium-channel-homologous-dsrna-restores-pyrethroid-insecticide-susceptibility-in-a-resistant-adult-mosquito-population
#17
Ana Caroline Dalla Bona, Rodrigo Faitta Chitolina, Marise Lopes Fermino, Lisiane de Castro Poncio, Avital Weiss, José Bento Pereira Lima, Nitzan Paldi, Emerson Soares Bernardes, Jonathan Henen, Eyal Maori
BACKGROUND: Mosquitoes host and pass on to humans a variety of disease-causing pathogens such as infectious viruses and other parasitic microorganisms. The emergence and spread of insecticide resistance is threatening the effectiveness of current control measures for common mosquito vector borne diseases, such as malaria, dengue and Zika. Therefore, the emerging resistance to the widely used pyrethroid insecticides is an alarming problem for public health. Herein we demonstrated the use of RNA interference (RNAi) to increase susceptibility of adult mosquitoes to a widely used pyrethroid insecticide...
2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27411529/rnai-mediated-knockdown-of-the-voltage-gated-sodium-ion-channel-tcnav-causes-mortality-in-tribolium-castaneum
#18
Hesham M Abd El Halim, Baida M H Alshukri, Munawar S Ahmad, Erich Y T Nakasu, Mohammed H Awwad, Elham M Salama, Angharad M R Gatehouse, Martin G Edwards
The voltage-gated sodium ion channel (VGSC) belongs to the largest superfamily of ion channels. Since VGSCs play key roles in physiological processes they are major targets for effective insecticides. RNA interference (RNAi) is widely used to analyse gene function, but recently, it has shown potential to contribute to novel strategies for selectively controlling agricultural insect pests. The current study evaluates the delivery of dsRNA targeted to the sodium ion channel paralytic A (TcNav) gene in Tribolium castaneum as a viable means of controlling this insect pest...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27327156/changes-in-the-expression-of-voltage-gated-sodium-channels-nav1-3-nav1-7-nav1-8-and-nav1-9-in-rat-trigeminal-ganglia-following-chronic-constriction-injury
#19
Wenhua Xu, Jun Zhang, Yuanyin Wang, Liecheng Wang, Xuxia Wang
Voltage-gated sodium channels (VGSCs), especially the tetrodotoxin-sensitive Nav1.3 and Nav1.7, and the tetrodotoxin-resistant Nav1.8 and Nav1.9, have been implicated in acute and chronic neuropathic pain. The aim of this study was to investigate the expression of VGSC Nav1.3, Nav1.7, Nav1.8, and Nav1.9 after nerve injury and their roles in the development of trigeminal neuralgia (TN). We used the infraorbital nerve-chronic constriction injury model of TN in the rat. The time course of changes in the mechanical pain threshold was examined...
August 17, 2016: Neuroreport
https://www.readbyqxmd.com/read/27307737/update-on-the-role-of-eslicarbazepine-acetate-in-the-treatment-of-partial-onset-epilepsy
#20
REVIEW
Renato Tambucci, Claudia Basti, Maria Maresca, Giangennaro Coppola, Alberto Verrotti
Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine - a dibenzazepine nucleus with the 5-carboxamide substituent, but is structurally different at the 10,11-position. ESL is a pro-drug metabolized to its major active metabolite eslicarbazepine. Despite the fact that the exact mechanism of action has not been fully elucidated, it is thought to involve inhibition of voltage-gated sodium channels (VGSC)...
2016: Neuropsychiatric Disease and Treatment
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