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https://www.readbyqxmd.com/read/28874684/damage-free-peripheral-nerve-stimulation-by-12-ns-pulsed-electric-field
#1
Maura Casciola, Shu Xiao, Andrei G Pakhomov
Modern technologies enable deep tissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28867800/ciguatoxins-evoke-potent-cgrp-release-by-activation-of-voltage-gated-sodium-channel-subtypes-nav1-9-nav1-7-and-nav1-1
#2
Filip Touska, Simon Sattler, Philipp Malsch, Richard J Lewis, Peter W Reeh, Katharina Zimmermann
Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1) into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP) from nerve terminals...
August 30, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28865490/mapping-insecticide-resistance-and-characterization-of-resistance-mechanisms-in-anopheles-arabiensis-diptera-culicidae-in-ethiopia
#3
Eba Alemayehu, Abebe Asale, Kasahun Eba, Kefelegn Getahun, Kora Tushune, Astrid Bryon, Evangelia Morou, John Vontas, Thomas Van Leeuwen, Luc Duchateau, Delenasaw Yewhalaw
BACKGROUND: The emergence and spread of insecticide resistance in the major African malaria vectors Anopheles gambiae (s.s.) and An. arabiensis may compromise the current vector control interventions and threatens the global malaria control and elimination efforts. METHODS: Insecticide resistance was monitored in several study sites in Ethiopia from 2013 to 2015 using papers impregnated with discriminating concentrations of DDT, deltamethrin, bendiocarb, propoxur, malathion, fenitrothion and pirimiphos-methyl, following the WHO insecticide susceptibility test procedure...
September 2, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28863150/a-single-markov-type-kinetic-model-accounting-for-the-macroscopic-currents-of-all-human-voltage-gated-sodium-channel-isoforms
#4
Pietro Balbi, Paolo Massobrio, Jeanette Hellgren Kotaleski
Modelling ionic channels represents a fundamental step towards developing biologically detailed neuron models. Until recently, the voltage-gated ion channels have been mainly modelled according to the formalism introduced by the seminal works of Hodgkin and Huxley (HH). However, following the continuing achievements in the biophysical and molecular comprehension of these pore-forming transmembrane proteins, the HH formalism turned out to carry limitations and inconsistencies in reproducing the ion-channels electrophysiological behaviour...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28831242/modeling-the-human-nav1-5-sodium-channel-structural-and-mechanistic-insights-of-ion-permeation-and-drug-blockade
#5
Marawan Ahmed, Horia Jalily Hasani, Aravindhan Ganesan, Michael Houghton, Khaled Barakat
Abnormalities in the human Nav1.5 (hNav1.5) voltage-gated sodium ion channel (VGSC) are associated with a wide range of cardiac problems and diseases in humans. Current structural models of hNav1.5 are still far from complete and, consequently, their ability to study atomistic interactions of this channel is very limited. Here, we report a comprehensive atomistic model of the hNav1.5 ion channel, constructed using homology modeling technique and refined through long molecular dynamics simulations (680 ns) in the lipid membrane bilayer...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28793859/investigating-knockdown-resistance-kdr-mechanism-against-pyrethroids-ddt-in-the-malaria-vector-anopheles-funestus-across-africa
#6
Helen Irving, Charles S Wondji
BACKGROUND: Understanding the molecular basis of insecticide resistance is key to improve the surveillance and monitoring of malaria vector populations under control. In the major malaria vector Anopheles funestus, little is currently known about the role of the knockdown resistance (kdr) mechanism. Here, we investigated the presence and contribution of knockdown resistance (kdr) to pyrethroids/DDT resistance observed in Anopheles funestus across Africa. RESULTS: Pyrosequencing genotyping and sequencing of the voltage gated sodium channel (VGSC) gene did not detect the common L1014F mutation in field collected An...
August 9, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28782435/rufinamide-pretreatment-attenuates-ischemia-reperfusion-injury-in-the-gerbil-hippocampus
#7
Chan Woo Park, Tae-Kyeong Lee, Jeong Hwi Cho, In Hye Kim, Jae-Chul Lee, Bich-Na Shin, Ji Hyeon Ahn, Sung Koo Kim, Myoung Cheol Shin, Taek Geun Ohk, Jun Hwi Cho, Moo-Ho Won, Young Joo Lee, Jeong Yeol Seo, Joon Ha Park
OBJECTIVES: Rufinamide, a voltage-gated sodium channel (VGSC) blocker, is widely used for the clinical treatment of seizures associated with Lennox-Gastaut syndrome. Previous studies have demonstrated that VGSC blockers have neuroprotective properties against ischemic damage following experimental cerebral ischemia. However, protective effects of rufinamide against cerebral ischemic insults have not been addressed. Therefore, in the present study, we firstly examined neuroprotective effects of rufinamide using a gerbil model of transient global cerebral ischemia...
August 7, 2017: Neurological Research
https://www.readbyqxmd.com/read/28734106/insecticide-resistance-in-trialeurodes-vaporariorum-populations-and-novel-diagnostics-for-kdr-mutations
#8
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
#9
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
#10
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...
August 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
#11
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
#12
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...
August 11, 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
#13
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
#14
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...
November 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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