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Voltage-gated sodium channel

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https://www.readbyqxmd.com/read/29776379/development-of-a-rapid-field-applicable-molecular-diagnostic-for-knockdown-resistance-kdr-markers-in-an-gambiae
#1
Vera T Unwin, Shaun Ainsworth, Emily J Rippon, El Hadji Amadou Niang, Mark J I Paine, David Weetman, Emily R Adams
BACKGROUND: The spread of insecticide resistance (IR) is a major threat to vector control programmes for mosquito-borne diseases. Early detection of IR using diagnostic markers could help inform these programmes, especially in remote locations where gathering reliable bioassay data is challenging. Most current molecular tests for genetic IR markers are only suitable for use in well-equipped laboratory settings. There is an unmet need for field-applicable diagnostics. METHODS: A single-cartridge test was designed to detect key IR mutations in the major African vector of malaria, Anopheles gambiae...
May 18, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29776361/emergence-of-knock-down-resistance-in-the-anopheles-gambiae-complex-in-the-upper-river-region-the-gambia-and-its-relationship-with-malaria-infection-in-children
#2
Anne L Wilson, Margaret Pinder, John Bradley, Martin J Donnelly, Majidah Hamid-Adiamoh, Lamin B S Jarju, Musa Jawara, David Jeffries, Ballah Kandeh, Emily J Rippon, Kolawole Salami, Umberto D'Alessandro, Steven W Lindsay
BACKGROUND: Insecticide resistance threatens malaria control in sub-Saharan Africa. Knockdown resistance to pyrethroids and organochlorines in Anopheles gambiae sensu lato (s.l.) is commonly caused by mutations in the gene encoding a voltage-gated sodium channel which is the target site for the insecticide. The study aimed to examine risk factors for knockdown resistance in An. gambiae s.l. and its relationship with malaria infection in children in rural Gambia. Point mutations at the Vgsc-1014 locus, were measured in An...
May 18, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29773519/the-neurosteroid-allopregnanolone-sulfate-inhibits-na-v-1-3-%C3%AE-subunit-containing-voltage-gated-sodium-channels-expressed-in-xenopus-oocytes
#3
Takafumi Horishita, Nobuyuki Yanagihara, Susumu Ueno, Dan Okura, Reiko Horishita, Tomoko Minami, Yuichi Ogata, Yuka Sudo, Yasuhito Uezono, Takashi Kawasaki
The neurosteroid allopregnanolone has potent analgesic effects, and its potential use for neuropathic pain is supported by recent reports. However, the analgesic mechanisms are obscure. The voltage-gated sodium channels (Nav ) α subunit Nav 1.3 is thought to play an essential role in neuropathic pain. Here, we report the effects of allopregnanolone sulfate (APAS) on sodium currents (INa ) in Xenopus oocytes expressing Nav 1.3 with β1 or β3 subunits. APAS suppressed INa of Nav 1.3 with β1 and β3 in a concentration-dependent manner (IC50 values; 75 and 26 μmol/L)...
March 30, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29770866/meucin-49-a-multifunctional-scorpion-venom-peptide-with-bactericidal-synergy-with-neurotoxins
#4
Bin Gao, Julie Dalziel, Simone Tanzi, Shunyi Zhu
Besides key roles in prey capture and predator defense, scorpion venom also functions as internal immune agents protecting the venom gland from infection and external immune agents cleaning saprophytic microbes from their own body surfaces. However, antimicrobials (typically antimicrobial peptides, AMPs) in the venom often exist in low abundance that might exclude their immune role alone, leaving an open question with regard to their in vivo biological function. Here, we report the bactericidal activity of seven peptides isolated from the scorpion Mesobuthus eupeus venom, including one classical α-helical AMP and five ion channel-targeted neurotoxins...
May 16, 2018: Amino Acids
https://www.readbyqxmd.com/read/29769724/structural-basis-for-gating-pore-current-in-periodic-paralysis
#5
Daohua Jiang, Tamer M Gamal El-Din, Christopher Ing, Peilong Lu, Régis Pomès, Ning Zheng, William A Catterall
Potassium-sensitive hypokalaemic and normokalaemic periodic paralysis are inherited skeletal muscle diseases characterized by episodes of flaccid muscle weakness1,2 . They are caused by single mutations in positively charged residues ('gating charges') in the S4 transmembrane segment of the voltage sensor of the voltage-gated sodium channel Nav 1.4 or the calcium channel Cav 1.11,2 . Mutations of the outermost gating charges (R1 and R2) cause hypokalaemic periodic paralysis1,2 by creating a pathogenic gating pore in the voltage sensor through which cations leak in the resting state3,4 ...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29757514/two-novel-mutations-in-the-voltage-gated-sodium-channel-associated-with-knockdown-resistance-kdr-in-the-dengue-vector-aedes-aegypti-in-vietnam
#6
Nguyen Thi Kim Lien, Nguyen Thi Hong Ngoc, Nguyen Thu Hien, Nguyen Huy Hoang, Nguyen Thi Huong Binh
No abstract text is available yet for this article.
June 2018: Journal of Vector Ecology: Journal of the Society for Vector Ecology
https://www.readbyqxmd.com/read/29748486/transcriptomic-analysis-of-ciguatoxin-induced-changes-in-gene-expression-in-primary-cultures-of-mice-cortical-neurons
#7
Juan Andrés Rubiolo, Carmen Vale, Andrea Boente-Juncal, Masahiro Hirama, Shuji Yamashita, Mercedes Camiña, Mercedes R Vieytes, Luis M Botana
Ciguatoxins are polyether marine toxins that act as sodium channel activators. These toxins cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents several symptoms in humans including long-term neurological alterations. Earlier work has shown that both acute and chronic exposure of primary cortical neurons to synthetic ciguatoxin CTX3C have profound impacts on neuronal function. Thus, the present work aimed to identify relevant neuronal genes and metabolic pathways that could be altered by ciguatoxin exposure...
May 10, 2018: Toxins
https://www.readbyqxmd.com/read/29744740/co-expression-of-%C3%AE-subunits-with-the-voltage-gated-sodium-channel-na-v-1-7-the-importance-of-subunit-association-and-phosphorylation-and-their-effects-on-channel-pharmacology-and-biophysics
#8
Maxim V Sokolov, Petra Henrich-Noack, Carina Raynoschek, Bo Franzén, Olof Larsson, Martin Main, Michael Dabrowski
The voltage-gated sodium ion channel NaV 1.7 is crucial in pain signaling. We examined how auxiliary β2 and β3 subunits and the phosphorylation state of the channel influence its biophysical properties and pharmacology. The human NaV 1.7α subunit was co-expressed with either β2 or β3 subunits in HEK-293 cells. The β2 subunits and the NaV 1.7α, however, were barely associated as evidenced by immunoprecipitation. Therefore, the β2 subunits did not change the biophysical properties of the channel. In contrast, β3 subunit was clearly associated with NaV 1...
May 10, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29740331/voltage-gated-sodium-channel-%C3%AE-1-%C3%AE-1b-subunits-regulate-cardiac-physiology-and-pathophysiology
#9
REVIEW
Nnamdi Edokobi, Lori L Isom
Cardiac myocyte contraction is initiated by a set of intricately orchestrated electrical impulses, collectively known as action potentials (APs). Voltage-gated sodium channels (NaV s) are responsible for the upstroke and propagation of APs in excitable cells, including cardiomyocytes. NaV s consist of a single, pore-forming α subunit and two different β subunits. The β subunits are multifunctional cell adhesion molecules and channel modulators that have cell type and subcellular domain specific functional effects...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29735899/determination-of-the-%C3%AE-conotoxin-piiia-specificity-against-voltage-gated-sodium-channels-from-binding-energy-calculations
#10
Fangling Chen, Wenxin Huang, Tao Jiang, Rilei Yu
Voltage-gated sodium (NaV ) channels generate and propagate action potentials in excitable cells, and several NaV subtypes have become important targets for pain management. The μ-conotoxins inhibit subtypes of the NaV with varied specificity but often lack of specificity to interested subtypes. Engineering the selectivity of the μ-conotoxins presents considerable complexity and challenge, as it involves the optimization of their binding affinities to multiple highly conserved NaV subtypes. In this study, a model of NaV 1...
May 7, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29728980/backbone-resonance-assignments-of-complexes-of-apo-human-calmodulin-bound-to-iq-motif-peptides-of-voltage-dependent-sodium-channels-na-v-1-1-na-v-1-4-and-na-v-1-7
#11
Holly M Isbell, Adina M Kilpatrick, Zesen Lin, Ryan Mahling, Madeline A Shea
Human voltage-gated sodium (NaV ) channels are critical for initiating and propagating action potentials in excitable cells. Nine isoforms have different roles but similar topologies, with a pore-forming α-subunit and auxiliary transmembrane β-subunits. NaV pathologies lead to debilitating conditions including epilepsy, chronic pain, cardiac arrhythmias, and skeletal muscle paralysis. The ubiquitous calcium sensor calmodulin (CaM) binds to an IQ motif in the C-terminal tail of the α-subunit of all NaV isoforms, and contributes to calcium-dependent pore-gating in some channels...
May 4, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29723302/preserved-scn4b-expression-is-an-independent-indicator-of-favorable-recurrence-free-survival-in-classical-papillary-thyroid-cancer
#12
Yanping Gong, Jing Yang, Wenshuang Wu, Feng Liu, Anping Su, Zhihui Li, Jingqiang Zhu, Tao Wei
Voltage-gated sodium channel β subunits (encoded by SCN1B to SCN4B genes) have been demonstrated as important multifunctional signaling molecules modulating cellular processes such as cell adhesion and cell migration. In this study, we aimed to explore the expression profiles of SCN4B in papillary thyroid cancer (PTC) and its prognostic value in terms of recurrence-free survival (RFS) in classical PTC. In addition, we also examined the potential effect of DNA methylation on its expression. A retrospective study was performed by using data from available large databases, including the Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA)-Thyroid Cancer (THCA)...
2018: PloS One
https://www.readbyqxmd.com/read/29723257/pharmacological-characterization-of-potent-and-selective-nav1-7-inhibitors-engineered-from-chilobrachys-jingzhao-tarantula-venom-peptide-jztx-v
#13
Bryan D Moyer, Justin K Murray, Joseph Ligutti, Kristin Andrews, Philippe Favreau, John B Jordan, Josie H Lee, Dong Liu, Jason Long, Kelvin Sham, Licheng Shi, Reto Stöcklin, Bin Wu, Ruoyuan Yin, Violeta Yu, Anruo Zou, Kaustav Biswas, Les P Miranda
Identification of voltage-gated sodium channel NaV1.7 inhibitors for chronic pain therapeutic development is an area of vigorous pursuit. In an effort to identify more potent leads compared to our previously reported GpTx-1 peptide series, electrophysiology screening of fractionated tarantula venom discovered the NaV1.7 inhibitory peptide JzTx-V from the Chinese earth tiger tarantula Chilobrachys jingzhao. The parent peptide displayed nominal selectivity over the skeletal muscle NaV1.4 channel. Attribute-based positional scan analoging identified a key Ile28Glu mutation that improved NaV1...
2018: PloS One
https://www.readbyqxmd.com/read/29722437/the-opioid-oxycodone-use-dependently-inhibits-the-cardiac-sodium-channel-nav1-5
#14
Jannis E Meents, Krisztina Juhasz, Sonja Stölzle-Feix, Vera Peuckmann-Post, Roman Rolke, Angelika Lampert
BACKGROUND AND PURPOSE: Oxycodone is a potent semi-synthetic opioid that is commonly used for the treatment of severe acute and chronic pain. However, treatment with oxycodone can lead to cardiac electrical changes, such as long-QT syndrome, potentially inducing sudden cardiac arrest. Here, we investigate whether the cardiac side effects of oxycodone can be explained by modulation of the cardiac sodium channel Nav1.5. EXPERIMENTAL APPROACH: Heterologously expressed Nav1...
May 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29722042/bicarbonate-refractory-qrs-prolongation-and-left-bundle-branch-block-following-escitalopram-and-lamotrigine-overdose-a-case-report-and-literature-review-of-toxic-left-bundle-branch-block
#15
A N Farkas, M Marcott, J H Yanta, A F Pizon
WHAT IS KNOWN AND OBJECTIVE: Toxic prolongation of the QRS interval most often results from blockade of cardiac voltage-gated sodium channels and manifests on electrocardiogram with a right bundle-branch block-like morphology. Rarely, a left bundle-branch block (LBBB) morphology has been reported. CASE REPORT: We report a case of transient LBBB resultant from ingestion of lamotrigine and citalopram which was refractory to sodium bicarbonate therapy and eventually resolved spontaneously...
May 2, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29719455/preemptive-application-of-qx-314-attenuates-trigeminal-neuropathic-mechanical-allodynia-in-rats
#16
Jeong-Ho Yoon, Jo-Young Son, Min-Ji Kim, Song-Hee Kang, Jin-Sook Ju, Yong-Chul Bae, Dong-Kuk Ahn
The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia...
May 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29719253/an-improved-method-for-modeling-voltage-gated-ion-channels-at-atomic-accuracy-applied-to-human-ca-v-channels
#17
Wilnelly Martinez-Ortiz, Timothy J Cardozo
Voltage-gated ion channels (VGICs) are associated with hundreds of human diseases. To date, 3D structural models of human VGICs have not been reported. We developed a 3D structural integrity metric to rank the accuracy of all VGIC structures deposited in the PDB. The metric revealed inaccuracies in structural models built from recent single-particle, non-crystalline cryo-electron microscopy maps and enabled the building of highly accurate homology models of human Cav channel α1 subunits at atomic resolution...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29712956/parallel-evolution-of-vgsc-mutations-at-domains-is6-iis6-and-iiis6-in-pyrethroid-resistant-aedes-aegypti-from-mexico
#18
Karla Saavedra-Rodriguez, Farah Vera Maloof, Corey L Campbell, Julian Garcia-Rejon, Audrey Lenhart, Patricia Penilla, Americo Rodriguez, Arturo Acero Sandoval, Adriana E Flores, Gustavo Ponce, Saul Lozano, William C Black
Aedes aegypti is the primary urban mosquito vector of viruses causing dengue, Zika and chikungunya fevers -for which vaccines and effective pharmaceuticals are still lacking. Current strategies to suppress arbovirus outbreaks include removal of larval-breeding sites and insecticide treatment of larval and adult populations. Insecticidal control of Ae. aegypti is challenging, due to a recent rapid global increase in knockdown-resistance (kdr) to pyrethroid insecticides. Widespread, heavy use of pyrethroid space-sprays has created an immense selection pressure for kdr, which is primarily under the control of the voltage-gated sodium channel gene (vgsc)...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29703751/gating-modifier-toxins-isolated-from-spider-venom-modulation-of-voltage-gated-sodium-channels-and-the-role-of-lipid-membranes
#19
Akello J Agwa, Steve Peigneur, Chun Yuen Chow, Nicole Lawrence, David J Craik, Jan Tytgat, Glenn F King, Sonia Troeira Henriques, Christina I Schroeder
Gating modifier toxins (GMTs) are venom-derived peptides isolated from spiders and other venomous creatures that modulate activity of disease-relevant voltage-gated ion channels and are therefore being pursued as therapeutic leads. The amphipathic surface profile of GMTs has prompted the proposal that some GMTs simultaneously bind to the cell membrane and voltage-gated ion channels in a trimolecular complex. Here we examined whether there is a relationship among spider GMT amphipathicity, membrane binding and potency or selectivity for voltage-gated sodium (NaV) channels...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29689688/swimming-exercise-induced-reversed-expression-of-mir-96-and-its-target-gene-nav1-3-in-diabetic-peripheral-neuropathy-in-rats
#20
Amir Mahmoudi Aghdam, Parviz Shahabi, Elham Karimi-Sales, Rafigheh Ghiasi, Saeed Sadigh-Eteghad, Javad Mahmoudi, Mohammad Reza Alipour
Diabetes is a common metabolic disease which leads to diabetic peripheral neuropathy. Recently, the role of microRNA-96 (miR-96) in alleviating neuropathic pain by inhibiting the expression of NaV1.3, an isoform of voltage-gated sodium channels, has been shown. Peripheral nerve injuries result in NaV1.3 elevation. Exercise has beneficial role in diabetes management and peripheral neuropathy. However, the effects of exercise on miR-96 and its target gene NaV1.3 in diabetic rats are unknown. Therefore, the present study investigated the effects of exercise training on the expression of miR-96 and NaV1...
April 25, 2018: Chinese Journal of Physiology
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