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Voltage-gated sodium channel

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https://www.readbyqxmd.com/read/28928441/effects-of-anti-epileptic-drugs-on-spreading-depolarization-induced-epileptiform-activity-in-mouse-hippocampal-slices
#1
Ching-Huei Lin, Shih-Pin Hsu, Ting-Chun Cheng, Chin-Wei Huang, Yao-Chang Chiang, I-Han Hsiao, Ming-Hsueh Lee, Mei-Lin Shen, Dong Chuan Wu, Ning Zhou
Epilepsy and spreading depolarization (SD) are both episodic brain disorders and often exist together in the same individual. In CA1 pyramidal neurons of mouse hippocampal slices, induction of SD evoked epileptiform activities, including the ictal-like bursts, which occurred during the repolarizing phase of SD, and the subsequent generation of paroxysmal depolarization shifts (PDSs), which are characterized by mild depolarization plateau with overriding spikes. The duration of the ictal-like activity was correlated with both the recovery time and the depolarization potential of SD, whereas the parameters of PDSs were not significantly correlated with the parameters of SD...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927993/voltage-gated-sodium-channel-%C3%AE-subunits-the-power-outside-the-pore-in-brain-development-and-disease
#2
REVIEW
Jacob M Hull, Lori L Isom
Voltage gated sodium channels (VGSCs) were first identified in terms of their role in the upstroke of the action potential. The underlying proteins were later identified as saxitoxin and scorpion toxin receptors consisting of α and β subunits. We now know that VGSCs are heterotrimeric complexes consisting of a single pore forming α subunit joined by two β subunits; a noncovalently linked β1 or β3 and a covalently linked β2 or β4 subunit. VGSC α subunits contain all the machinery necessary for channel cell surface expression, ion conduction, voltage sensing, gating, and inactivation, in one central, polytopic, transmembrane protein...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28925040/thermal-melt-circular-dichroism-spectroscopic-studies-for-identifying-stabilising-amphipathic-molecules-for-the-voltage-gated-sodium-channel-navms
#3
Sam M Ireland, Altin Sula, B A Wallace
Purified integral membrane proteins require amphipathic molecules to maintain their solubility in aqueous solutions. These complexes, in turn, are used in studies to characterise the protein structures by a variety of biophysical and structural techniques, including spectroscopy, crystallography, and cryo-electron microscopy. Typically the amphilphiles used have been detergent molecules, but more recently they have included amphipols, which are polymers of different sizes and compositions designed to create smaller, more well-defined solubilised forms of the membrane proteins...
September 19, 2017: Biopolymers
https://www.readbyqxmd.com/read/28922053/distribution-and-function-of-voltage-gated-sodium-channels-in-the-nervous-system
#4
Jun Wang, Shao-Wu Ou, Yun-Jie Wang
Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases...
September 18, 2017: Channels
https://www.readbyqxmd.com/read/28916354/abnormal-sodium-channel-mrna-splicing-in-hypertrophic-cardiomyopathy
#5
Adam M Noyes, Anyu Zhou, Ge Gao, Lianzhi Gu, Sharlene Day, J Andrew Wasserstrom, Samuel C Dudley
BACKGROUND: Our previous studies showed that in ischemic and nonischemic heart failure (HF), the voltage-gated cardiac Na(+) channel α subunit (SCN5A) mRNA is abnormally spliced to produce two truncated transcript variants (E28C and D) that activate the unfolded protein response (UPR). We tested whether SCN5A post-transcriptional regulation was abnormal in hypertrophic cardiomyopathy (HCM). MATERIAL AND METHODS: Human heart tissue was obtained from HCM patients...
September 7, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28915149/bulleyaconitine-a-preferably-reduces-tetrodotoxin-sensitive-sodium-current-in-uninjured-dorsal-root-ganglion-neurons-of-neuropathic-rats-probably-via-inhibition-of-protein-kinase-c
#6
Man-Xiu Xie, Rui-Ping Pang, Jie Yang, Kai-Feng Shen, Jing Xu, Xiong-Xiong Zhong, Shao-Kun Wang, Xiao-Long Zhang, Yan-Qing Liu, Xian-Guo Liu
Oral Bulleyaconitine A (BLA) is effective for treating neuropathic pain in human patients, but the underlying mechanism is poorly understood. Here, we tested whether BLA blocked voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons. Compelling evidence shows that voltage-gated sodium channels are upregulated in uninjured DRG neurons but downregulated in injured ones following peripheral nerve injury. We found that BLA preferably inhibited Na currents in uninjured DRG neurons in neuropathic rats...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28910154/activation-of-veratridine-sensitive-sodium-channels-but-not-electrical-field-stimulation-dilates-porcine-retinal-arterioles-with-preserved-perivascular-tissue
#7
Nils M Kratholm, Peter Skov Jensen, Sidse Kringelholt, Ulf Simonsen, Toke Bek
PURPOSE: Disturbances in retinal blood flow are a prominent feature of vision threatening retinal diseases. The regulation of tone in retinal resistance vessels involves the perivascular retinal tissue, but it is unknown to what extent neurons or glial cells contribute to the effect. Therefore, the purpose of the present study was to study the contribution of neurons in the perivascular retina to vascular tone during activation of voltage-gated sodium channels with veratridine and electrical field stimulation (EFS)...
September 14, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28905186/antidepressants-inhibit-nav1-3-nav1-7-and-nav1-8-neuronal-voltage-gated-sodium-channels-more-potently-than-nav1-2-and-nav1-6-channels-expressed-in-xenopus-oocytes
#8
Takafumi Horishita, Nobuyuki Yanagihara, Susumu Ueno, Dan Okura, Reiko Horishita, Tomoko Minami, Yuichi Ogata, Yuka Sudo, Yasuhito Uezono, Takeyoshi Sata, Takashi Kawasaki
Tricyclic antidepressants (TCAs) and duloxetine are used to treat neuropathic pain. However, the mechanisms underlying their analgesic effects remain unclear. Although many investigators have shown inhibitory effects of antidepressants on voltage-gated sodium channels (Nav) as a possible mechanism of analgesia, to our knowledge, no one has compared effects on the diverse variety of sodium channel α subunits. We investigated the effects of antidepressants on sodium currents in Xenopus oocytes expressing Nav1...
September 14, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28904093/sodium-dynamics-in-pyramidal-neuron-dendritic-spines-synaptically-evoked-entry-predominantly-through-ampa-receptors-and-removal-by-diffusion
#9
Kenichi Miyazaki, William N Ross
Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties with newly developed simultaneous sodium and calcium imaging that had single spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high speed, low noise CCD camera...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28898267/depolarization-of-the-conductance-voltage-relationship-in-the-nav1-5-mutant-e1784k-is-due-to-altered-fast-inactivation
#10
Colin H Peters, Alec Yu, Wandi Zhu, Jonathan R Silva, Peter C Ruben
E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors...
2017: PloS One
https://www.readbyqxmd.com/read/28894008/genetic-disruption-of-ankyrin-g-in-adult-mouse-forebrain-causes-cortical-synapse-alteration-and-behavior-reminiscent-of-bipolar-disorder
#11
Shanshan Zhu, Zachary A Cordner, Jiali Xiong, Chi-Tso Chiu, Arabiye Artola, Yanning Zuo, Andrew D Nelson, Tae-Yeon Kim, Natalya Zaika, Brian M Woolums, Evan J Hess, Xiaofang Wang, De-Maw Chuang, Mikhail M Pletnikov, Paul M Jenkins, Kellie L Tamashiro, Christopher A Ross
Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28880078/the-role-of-disulfide-bond-replacements-in-analogues-of-the-tarantula-toxin-protx-ii-and-their-effects-on-inhibition-of-the-voltage-gated-sodium-ion-channel-nav1-7
#12
Zoë V F Wright, Stephen McCarthy, Rachael Dickman, Francis E Reyes, Silvia Sanchez-Martinez, Adam Cryar, Ian Kilford, Adrian Hall, Andrew K Takle, Maya Topf, Tamir Gonen, Konstantinos Thalassinos, Alethea B Tabor
Spider venom toxins, such as Protoxin-II (ProTx-II), have recently received much attention as selective Nav1.7 channel blockers, with potential to be developed as leads for the treatment of chronic nocioceptive pain. ProTx-II is a 30-amino acid peptide with three disulfide bonds that has been reported to adopt a well-defined inhibitory cystine knot (ICK) scaffold structure. Potential drawbacks with such peptides include poor pharmacodynamics and potential scrambling of the disulfide bonds in vivo. In order to address these issues, in the present study we report the solid-phase synthesis of lanthionine-bridged analogues of ProTx-II, in which one of the three disulfide bridges is replaced with a thioether linkage, and evaluate the biological properties of these analogues...
September 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28874684/damage-free-peripheral-nerve-stimulation-by-12-ns-pulsed-electric-field
#13
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/28871036/sodium-channel-%C3%AE-2-subunits-prevent-action-potential-propagation-failures-at-axonal-branch-points
#14
In Ha Cho, Lauren C Panzera, Morven Chin, Michael B Hoppa
Neurotransmitter release depends on voltage-gated Na(+) channels (Navs) to successfully propagate an action potential (AP) from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na(+) channels. Using optical recordings of Ca(2+) and membrane voltage, we demonstrate that Na(+) channel β2 subunits (Navβ2) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female)...
September 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#15
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
#16
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
#17
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/28854259/arizona-bark-scorpion-venom-resistance-in-the-pallid-bat-antrozous-pallidus
#18
Bradley H Hopp, Ryan S Arvidson, Michael E Adams, Khaleel A Razak
The pallid bat (Antrozous pallidus), a gleaning bat found in the western United States and Mexico, hunts a wide variety of ground-dwelling prey, including scorpions. Anecdotal evidence suggests that the pallid bat is resistant to scorpion venom, but no systematic study has been performed. Here we show with behavioral measures and direct injection of venom that the pallid bat is resistant to venom of the Arizona bark scorpion, Centruroides sculpturatus. Our results show that the pallid bat is stung multiple times during a hunt without any noticeable effect on behavior...
2017: PloS One
https://www.readbyqxmd.com/read/28845834/clinical-stabilisation-with-lacosamide-of-mood-disorder-comorbid-with-ptsd-and-fronto-temporal-epilepsy
#19
Ilaria Cuomo, Georgios D Kotzalidis, Sergio De Filippis
BACKGROUND AND AIM OF THE WORK: Mood disorders are often complicated by comorbidity with epilepsy. Anxiety and personality disorders may worsen prognosis and treatment outcome. Lacosamide has been recently introduced as adjunctive treatment for partial epilepsy. Its mechanism consists of selective slow inactivation of voltage-gated sodium channels, thus promoting an extended stabilisation of cell membranes. Antiepileptic drugs have been largely used since the 1950s in psychiatry as mood stabilisers due to their membrane stabilising and anti-kindling effects...
August 23, 2017: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/28842554/cdyl-suppresses-epileptogenesis-in-mice-through-repression-of-axonal-nav1-6-sodium-channel-expression
#20
Yongqing Liu, Shirong Lai, Weining Ma, Wei Ke, Chan Zhang, Shumeng Liu, Yu Zhang, Fei Pei, Shaoyi Li, Ming Yi, Yousheng Shu, Yongfeng Shang, Jing Liang, Zhuo Huang
Impairment of intrinsic plasticity is involved in a range of neurological disorders such as epilepsy. However, how intrinsic excitability is regulated is still not fully understood. Here we report that the epigenetic factor Chromodomain Y-like (CDYL) protein is a critical regulator of the initiation and maintenance of intrinsic neuroplasticity by regulating voltage-gated ion channels in mouse brains. CDYL binds to a regulatory element in the intron region of SCN8A and mainly recruits H3K27me3 activity for transcriptional repression of the gene...
August 25, 2017: Nature Communications
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