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https://www.readbyqxmd.com/read/28734106/insecticide-resistance-in-trialeurodes-vaporariorum-populations-and-novel-diagnostics-for-kdr-mutations
#1
Despoina Evr Kapantaidaki, Eldem Sadikoglou, Dimitra Tsakireli, Vasileios Kampanis, Marianna Stavrakaki, Corinna Schorn, Aris Ilias, Maria Riga, George Tsiamis, Ralf Nauen, George Skavdis, John Vontas, Anastasia Tsagkarakou
BACKGROUND: Neonicotinoids, pyrethroids and ketoenols, are currently used for the control of Trialeurodes vaporariorum (Hemiptera: Aleyrodidae). In this study, insecticide resistance status and mechanisms were investigated by classical bioassays and molecular techniques. RESULTS: Dose response bioassays were performed on 19 Greek populations, among the 35 different whitefly populations used for the whole analysis. Resistance factors scaled up to 207-, 4657- and 59- fold, for imidacloprid, bifenthrin and spiromesifen, respectively...
July 22, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28725028/detection-and-quantitation-of-copy-number-variation-in-the-voltage-gated-sodium-channel-gene-of-the-mosquito-culex-quinquefasciatus
#2
Walter Fabricio Silva Martins, Krishanthi Subramaniam, Keith Steen, Henry Mawejje, Triantafillos Liloglou, Martin James Donnelly, Craig Stephen Wilding
Insecticide resistance is typically associated with alterations to the insecticidal target-site or with gene expression variation at loci involved in insecticide detoxification. In some species copy number variation (CNV) of target site loci (e.g. the Ace-1 target site of carbamate insecticides) or detoxification genes has been implicated in the resistance phenotype. We show that field-collected Ugandan Culex quinquefasciatus display CNV for the voltage-gated sodium channel gene (Vgsc), target-site of pyrethroid and organochlorine insecticides...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698102/neonatal-nav1-5-protein-expression-in-normal-adult-human-tissues-and-breast-cancer
#3
Rezan Fahrioglu Yamaci, Scott P Fraser, Esra Battaloglu, Handan Kaya, Kamil Erguler, Christopher S Foster, Mustafa B A Djamgoz
Expression of the neonatal splice variant of the voltage-gated sodium channel α-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel(®)in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28679467/effects-of-a-novel-sodium-channel-blocker-gsk2339345-in-patients-with-refractory-chronic-cough%C3%A2
#4
Jaclyn A Smith, Lorcan P A McGarvey, Huda Badri, Imran Satia, Francis Warren, Sarah Siederer, Lia Liefaard, Robert D Murdoch, Kathryn Povey, Joanna Marks-Konczalik
OBJECTIVE: Voltage-gated sodium channels (VGSC) are important in the initiation and propagation of action potentials in afferent sensory nerve fibers responsible for evoking cough. This study investigated the efficacy of GSK2339345, a VGSC inhibitor, in the treatment of refractory chronic cough (RCC). METHODS: A three-part randomized, double-blind, placebo-controlled, cross-over study was conducted in the UK. In part A, patients with RCC received two inhaled doses of either GSK2339345 or placebo, 4 hours apart during three study periods...
July 6, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28655765/parallel-homodimer-structures-of-the-extracellular-domains-of-the-voltage-gated-sodium-channel-%C3%AE-4-subunit-explain-its-role-in-cell-cell-adhesion
#5
Hideaki Shimizu, Asako Tosaki, Noboru Ohsawa, Yoshiko Ishizuka-Katsura, Shisako Shoji, Haruko Miyazaki, Fumitaka Oyama, Takaho Terada, Mikako Shirouzu, Shun-Ichi Sekine, Nobuyuki Nukina, Shigeyuki Yokoyama
Voltage-gated sodium channels (VGSCs) are transmembrane proteins required for the generation of action potentials in excitable cells and essential for propagating electrical impulses along nerve cells. VGSCs are complexes of a pore-forming α subunit and auxiliary β subunits, designated as β1/β1B-β4 (encoded by SCN1B-4B, respectively), which also function in cell-cell adhesion. We previously reported the structural basis for the trans homophilic interaction of the β4 subunit, which contributes to its adhesive function...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28608751/molecular-modelling-studies-of-kdr-mutations-in-voltage-gated-sodium-channel-revealed-significant-conformational-variations-contributing-to-insecticide-resistance
#6
Nanda Kumar Yellapu, Jeyakodi Gopal, Gunasekaran Kasinahtan, Jambulingam Purushothaman
Voltage gated sodium channels (VGSC) of mosquito vectors are the primary targets of DDT and other synthetic pyrethroids used in public health programs. The knockdown resistant (kdr) mutations in VGSC are associated with the insecticide resistance especially in Anophelines. The present study is aimed to emphasize and demarcate the impact of three kdr-mutations such as L1014S, L1014F and L1014H on insecticide resistance. The membrane model of sodium transport domain of VGSC (STD-VGSC) was constructed using de novo approach based on domain and trans-membrane predictions...
June 13, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28591591/activation-of-sodium-channel-by-a-novel-%C3%AE-scorpion-toxin-bmk-nt2-stimulates-erk1-2-and-cerb-phosphorylation-through-a-ca-2-dependent-pathway-in-neocortical-neurons
#7
Xiaohan Zou, Ying Wu, Juan Chen, Fang Zhao, Fan Zhang, Boyang Yu, Zhengyu Cao
Neuronal excitability controls the expression of a variety of genes and proteins and therefore regulates neurite outgrowth and synapse formation, fundamental physiological processes controlling learning and memory. Scorpion venom contains many neurotoxins which alter ion channel activities that influence neuronal excitability. In this study, a novel scorpion peptide termed BmK NT2 was purified from venom of Chinese scorpion Buthus martensii Karsch by combining mass spectrum mapping and intracellular Ca(2+) concentration measurement in primary cultured neocortical neurons...
June 4, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28591378/is-there-a-role-for-voltage-gated-na-channels-in-the-aggressiveness-of-breast-cancer
#8
P Rhana, R R Trivelato, P S L Beirão, J S Cruz, A L P Rodrigues
Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness...
June 5, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28583207/knockdown-resistance-kdr-of-the-voltage-gated-sodium-channel-gene-of-aedes-aegypti-population-in-denpasar-bali-indonesia
#9
Penny Humaidah Hamid, Joko Prastowo, Anis Widyasari, Anja Taubert, Carlos Hermosilla
BACKGROUND: Aedes aegypti is the main vector of several arthropod-borne viral infections in the tropics profoundly affecting humans, such as dengue fever (DF), West Nile (WN), chikungunya and more recently Zika. Eradication of Aedes still largely depends on insecticides, which is the most cost-effective strategy, and often inefficient due to resistance development in exposed Aedes populations. We here conducted a study of Ae. aegypti resistance towards several insecticides regularly used in the city of Denpasar, Bali, Indonesia...
June 5, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28464338/new-anti-seizure-arylalkyl-azole-derivatives-synthesis-in-vivo-and-in-silico-studies
#10
Suat Sari, Sevim Dalkara, Filiz Betül Kaynak, Jóhannes Reynisson, Selma Saraç, Arzu Karakurt
(Arylalkyl)azoles are a class of antiepileptic compounds including nafimidone, denzimol, and loreclezole (LRZ). Nafimidone and denzimol are thought to inhibit voltage-gated sodium channels (VGSCs) and enhance γ-aminobutyric acid (GABA)-mediated response. LRZ, a positive allosteric modulator of A-type GABA receptors (GABAA Rs), was reported to be sensitive to Asn265 of the β2/β3 subunit. Here, we report new N-[1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethylidene]hydroxylamine esters showing anticonvulsant activity in animal models, including the 6-Hz psychomotor seizure test, a model for therapy-resistant partial seizure...
June 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28432032/neuronal-excitation-and-permeabilization-by-200-ns-pulsed-electric-field-an-optical-membrane-potential-study-with-fluovolt-dye
#11
Andrei G Pakhomov, Iurii Semenov, Maura Casciola, Shu Xiao
Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca(2+) signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within <1ms...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28414744/knockdown-resistance-mutations-predict-ddt-resistance-and-pyrethroid-tolerance-in-the-visceral-leishmaniasis-vector-phlebotomus-argentipes
#12
Bruno Gomes, Bidyut Purkait, Rinki Michelle Deb, Aarti Rama, Rudra Pratap Singh, Geraldine Marie Foster, Michael Coleman, Vijay Kumar, Mark Paine, Pradeep Das, David Weetman
BACKGROUND: Indoor residual spraying (IRS) with DDT has been the primary strategy for control of the visceral leishmaniasis (VL) vector Phlebotomus argentipes in India but efficacy may be compromised by resistance. Synthetic pyrethroids are now being introduced for IRS, but with a shared target site, the para voltage-gated sodium channel (VGSC), mutations affecting both insecticide classes could provide cross-resistance and represent a threat to sustainable IRS-based disease control. METHODOLOGY/PRINCIPAL FINDINGS: A region of the Vgsc gene was sequenced in P...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28373025/early-life-febrile-seizures-worsen-adult-phenotypes-in-scn1a-mutants
#13
Stacey B B Dutton, Karoni Dutt, Ligia A Papale, Sandra Helmers, Alan L Goldin, Andrew Escayg
Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A, encoding the Nav1.1 channel, are responsible for a number of epilepsy disorders including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS). Patients with SCN1A mutations often experience prolonged early-life febrile seizures (FSs), raising the possibility that these events may influence epileptogenesis and lead to more severe adult phenotypes. To test this hypothesis, we subjected 21-23-day-old mice expressing the human SCN1A GEFS+ mutation R1648H to prolonged hyperthermia, and then examined seizure and behavioral phenotypes during adulthood...
July 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28359334/cytokine-cascades-induced-by-mechanical-trauma-injury-alter-voltage-gated-sodium-channel-activity-in-intact-cortical-neurons
#14
Weiqiang Chen, Jiangtao Sheng, Jingfang Guo, Guoyi Peng, Jinfang Hong, Bingbing Li, Xiaoxuan Chen, Kangsheng Li, Shousen Wang
BACKGROUND: Traumatic brain injury (TBI) triggers both immediate (primary) and long-term (secondary) tissue damages. Secondary damages can last from hours to days or even a lifetime. Secondary damages implicate several mechanisms, including influence of inflammatory mediators, mainly cytokines, on excitability of ion channels. However, studies should further explore the effects of inflammatory cytokines on voltage-gated sodium channels (VGSCs) and excitability in distal intact neurons...
March 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28347465/zn-2-reduction-induces-neuronal-death-with-changes-in-voltage-gated-potassium-and-sodium-channel-currents
#15
Kun Tian, Cong-Cong He, Hui-Nan Xu, Yu-Xiang Wang, Hong-Gang Wang, Di An, Bin Heng, Wei Pang, Yu-Gang Jiang, Yan-Qiang Liu
In the present study, cultured rat primary neurons were exposed to a medium containing N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a specific cell membrane-permeant Zn(2+) chelator, to establish a model of free Zn(2+) deficiency in neurons. The effects of TPEN-mediated free Zn(2+) ion reduction on neuronal viability and on the performance of voltage-gated sodium channels (VGSCs) and potassium channels (Kvs) were assessed. Free Zn(2+) deficiency 1) markedly reduced the neuronal survival rate, 2) reduced the peak amplitude of INa, 3) shifted the INa activation curve towards depolarization, 4) modulated the sensitivity of sodium channel voltage-dependent inactivation to a depolarization voltage, and 5) increased the time course of recovery from sodium channel inactivation...
May 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28347352/combined-target-site-kdr-mutations-play-a-primary-role-in-highly-pyrethroid-resistant-phenotypes-of-aedes-aegypti-from-saudi-arabia
#16
Ashwaq M Al Nazawi, Jabir Aqili, Mohammed Alzahrani, Philip J McCall, David Weetman
BACKGROUND: Pyrethroid resistance is a threat to effective vector control of Aedes aegypti, the vector of dengue, Zika and other arboviruses, but there are many major knowledge gaps on the mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control but information about resistance remains sparse, and the underlying genetic basis is unknown. Findings from an ongoing study in this internationally significant area are reported here...
March 27, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28338073/veratridine-produces-distinct-calcium-response-profiles-in-mouse-dorsal-root-ganglia-neurons
#17
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
#18
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
#19
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
#20
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
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