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Voltage-gated sodium channel

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https://www.readbyqxmd.com/read/29356177/proline-rich-transmembrane-protein-2-negative-paroxysmal-kinesigenic-dyskinesia-clinical-and-genetic-analyses-of-163-patients
#1
Wo-Tu Tian, Xiao-Jun Huang, Xiao Mao, Qing Liu, Xiao-Li Liu, Sheng Zeng, Xia-Nan Guo, Jun-Yi Shen, Yang-Qi Xu, Hui-Dong Tang, Xiao-Meng Yin, Mei Zhang, Wei-Guo Tang, Xiao-Rong Liu, Bei-Sha Tang, Sheng-Di Chen, Li Cao
BACKGROUND: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. OBJECTIVE: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia. METHODS: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel...
January 22, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29355592/down-regulation-of-inwardly-rectifying-k-currents-in-astrocytes-derived-from-patients-with-monge-s-disease
#2
Wei Wu, Hang Yao, Helen W Zhao, Juan Wang, Gabriel G Haddad
Chronic mountain sickness (CMS) or Monge's disease is a disease in highlanders. These patients have a variety of neurologic symptoms such as migraine, mental fatigue, confusion, dizziness, loss of appetite, memory loss and neuronal degeneration. The cellular and molecular mechanisms underlying CMS neuropathology is not understood. In the previous study, we demonstrated that neurons derived from CMS patients' fibroblasts have a decreased expression and altered gating properties of voltage-gated sodium channel...
January 17, 2018: Neuroscience
https://www.readbyqxmd.com/read/29344121/a-five-gene-based-risk-score-with-high-prognostic-value-in-colorectal-cancer
#3
Yida Pan, Hongyang Zhang, Mingming Zhang, Jie Zhu, Jianghong Yu, Bangting Wang, Jigang Qiu, Jun Zhang
Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29340775/global-versus-local-mechanisms-of-temperature-sensing-in-ion-channels
#4
REVIEW
Cristina Arrigoni, Daniel L Minor
Ion channels turn diverse types of inputs, ranging from neurotransmitters to physical forces, into electrical signals. Channel responses to ligands generally rely on binding to discrete sensor domains that are coupled to the portion of the channel responsible for ion permeation. By contrast, sensing physical cues such as voltage, pressure, and temperature arises from more varied mechanisms. Voltage is commonly sensed by a local, domain-based strategy, whereas the predominant paradigm for pressure sensing employs a global response in channel structure to membrane tension changes...
January 17, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29337221/venom-characterization-of-the-amazonian-scorpion-tityus-metuendus
#5
C V F Batista, J G Martins, R Restano-Cassulini, F I V Coronas, F Z Zamudio, R Procópio, L D Possani
The soluble venom from the scorpion Tityus metuendus was characterized by various methods. In vivo experiments with mice showed that it is lethal. Extended electrophysiological recordings using seven sub-types of human voltage gated sodium channels (hNav1.1 to 1.7) showed that it contains both α- and β-scorpion toxin types. Fingerprint analysis by mass spectrometry identified over 200 distinct molecular mass components. At least 60 sub-fractions were recovered from HPLC separation. Five purified peptides were sequenced by Edman degradation, and their complete primary structures were determined...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29337050/impairments-in-social-novelty-recognition-and-spatial-memory-in-mice-with-conditional-deletion-of-scn1a-in-parvalbumin-expressing-cells
#6
Tetsuya Tatsukawa, Ikuo Ogiwara, Emi Mazaki, Atsushi Shimohata, Kazuhiro Yamakawa
Loss of function mutations in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1, have been described in the majority of Dravet syndrome patients presenting with epileptic seizures, hyperactivity, autistic traits, and cognitive decline. We previously reported predominant Nav1.1 expression in parvalbumin-expressing (PV+) inhibitory neurons in juvenile mouse brain and observed epileptic seizures in mice with selective deletion of Scn1a in PV+ cells mediated by PV-Cre transgene expression (Scn1afl/+/PV-Cre-TG)...
January 11, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29335582/differential-roles-of-nav1-2-and-nav1-6-in-regulating-neuronal-excitability-at-febrile-temperature-and-distinct-contributions-to-febrile-seizures
#7
Mingyu Ye, Jun Yang, Cuiping Tian, Qiyu Zhu, Luping Yin, Shan Jiang, Mingpo Yang, Yousheng Shu
Dysregulation of voltage-gated sodium channels (VGSCs) is associated with multiple clinical disorders, including febrile seizures (FS). The contribution of different sodium channel subtypes to environmentally triggered seizures is not well understood. Here we demonstrate that somatic and axonal sodium channels primarily mediated through NaV1.2 and NaV1.6 subtypes, respectively, behave differentially at FT, and might play distinct roles in FS generation. In contrast to sodium channels on the main axonal trunk, somatic ones are more resistant to inactivation and display significantly augmented currents, faster gating rates and kinetics of recovery from inactivation at FT, features that promote neuronal excitabilities...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29335280/mapping-protein-interactions-of-sodium-channel-nav1-7-using-epitope-tagged-gene-targeted-mice
#8
Alexandros H Kanellopoulos, Jennifer Koenig, Honglei Huang, Martina Pyrski, Queensta Millet, Stéphane Lolignier, Toru Morohashi, Samuel J Gossage, Maude Jay, John E Linley, Georgios Baskozos, Benedikt M Kessler, James J Cox, Annette C Dolphin, Frank Zufall, John N Wood, Jing Zhao
The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo The sodium channel β3 (Scn3b), rather than the β1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing-response mediator protein (Crmp2) and Nav1...
January 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29318638/voltage-gated-sodium-channels-nav-igating-the-field-to-determine-their-contribution-to-visceral-nociception
#9
Andelain Erickson, Annemie Deiteren, Andrea M Harrington, Sonia Garcia-Caraballo, Joel Castro, Ashlee Caldwell, Luke Grundy, Stuart M Brierley
Chronic visceral pain, altered motility and bladder dysfunction are common, yet poorly managed symptoms of functional and inflammatory disorders of the gastrointestinal and urinary tracts. Recently, numerous human channelopathies of the voltage-gated sodium (NaV ) channel family have been identified, which induce either painful neuropathies, an insensitivity to pain, or alterations in smooth muscle function. The identification of these disorders, in addition to the recent utilisation of genetically modified NaV mice and specific NaV channel modulators, has shed new light on how NaV channels contribute to the function of neuronal and non-neuronal tissues within the gastrointestinal tract and bladder...
January 9, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29313492/rufinamide-for-the-treatment-of-lennox-gastaut-syndrome-evidence-from-clinical-trials-and-clinical-practice
#10
Pasquale Striano, Rob McMurray, Estevo Santamarina, Mercè Falip
Rufinamide was granted orphan drug status in 2004 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients aged ≥4 years, and was subsequently approved for this indication in several countries, including Europe and the United States. Structurally unrelated to other antiepileptic drugs, rufinamide is thought to act primarily by prolonging the inactivation phase of voltage-gated sodium channels. Rufinamide was approved on the basis of an international, randomised, placebo-controlled Phase III trial, conducted in 138 patients with Lennox-Gastaut syndrome, which demonstrated its favourable tolerability profile and efficacy in significantly reducing the frequency of drop attacks and total seizures, compared with placebo...
January 9, 2018: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/29306662/ciguatoxins-activate-the-calcineurin-signalling-pathway-in-yeasts-potential-for-development-of-an-alternative-detection-tool
#11
Hélène Martin-Yken, Camille Gironde, Sylvain Derick, Hélène Taiana Darius, Christophe Furger, Dominique Laurent, Mireille Chinain
Ciguatoxins (CTXs) are lipid-soluble polyether compounds produced by dinoflagellates from the genus Gambierdiscus spp. typically found in tropical and subtropical zones. This endemic area is however rapidly expanding due to environmental perturbations, and both toxic Gambierdiscus spp. and ciguatoxic fishes have been recently identified in the North Atlantic Ocean (Madeira and Canary islands) and Mediterranean Sea. Ciguatoxins bind to Voltage Gated Sodium Channels on the membranes of sensory neurons, causing Ciguatera Fish Poisoning (CFP) in humans, a disease characterized by a complex array of gastrointestinal, neurological, neuropsychological, and cardiovascular symptoms...
January 4, 2018: Environmental Research
https://www.readbyqxmd.com/read/29288635/foxd3-inhibits-scn2a-gene-transcription-in-intractable-epilepsy-cell-models
#12
Jun Xiang, Fang Wen, Lingyun Zhang, Yu Zhou
The expression of sodium voltage-gated channel alpha subunit 2 (SCN2A) is closely related to the development of epilepsy. This study investigated regulatory element of the SCN2A gene involved in epilepsy. An intractable epilepsy cell model was constructed using hippocampal primary neurons and the SH-SY5Y cell line. SCN2A protein and gene expression in cells as well as the level of lactic acid dehydrogenase (LDH) in the cell culture supernatants was detected. Potential regulatory factors of SCN2A and its upstream regulatory elements were identified using the dual-luciferase reporter assay...
December 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29274536/are-there-fitness-costs-of-adaptive-pyrethroid-resistance-in-the-amphipod-hyalella-azteca
#13
Jennifer R Heim, Donald P Weston, Kaley Major, Helen Poynton, Kara E Huff Hartz, Michael J Lydy
Pyrethroid-resistant Hyalella azteca with voltage-gated sodium channel mutations have been identified at multiple locations throughout California. In December 2013, H. azteca were collected from Mosher Slough in Stockton, CA, USA, a site with reported pyrethroid (primarily bifenthrin and cyfluthrin) sediment concentrations approximately twice the 10-d LC50 for laboratory-cultured H. azteca. These H. azteca were shipped to Southern Illinois University Carbondale and have been maintained in pyrethroid-free culture since collection...
December 20, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29262297/antiallodynic-and-antihyperalgesic-activity-of-new-3-3-diphenyl-propionamides-with-anticonvulsant-activity-in-models-of-pain-in-mice
#14
Anna Rapacz, Jolanta Obniska, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Agata Siwek, Anna Gryboś, Sabina Rybka, Aleksandra Karcz, Elżbieta Pękala, Barbara Filipek
Anticonvulsant drugs are used to treat a wide range of non-epileptic conditions, including chronic pain. The aim of the present experiments was to examine analgesic activity of three new 3,3-diphenyl-propionamides, which had previously demonstrated anticonvulsant activity in the MES (maximal electroshock seizure), scPTZ (subcutaneous pentylenetetrazole) and/or 6Hz (psychomotor seizure) tests in mice. Antinociceptive activity was examined in mouse models of acute pain (the hot plate test) and tonic pain (the formalin test) in mice...
December 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29248843/modulation-of-voltage-gated-sodium-channels-induces-capacitation-in-bull-spermatozoa-through-phosphorylation-of-tyrosine-containing-proteins
#15
Dharmendra Singh Chauhan, Dilip Kumar Swain, Nadeem Shah, Hanuman Prasad Yadav, Abhishek Sharma, Brijesh Yadav, Sarvajeet Yadav, Rajesh Nigam, Satish Kumar Garg
In our previous study, we have reported the molecular presence of Nav 1.8 in bull spermatozoa and its potential involvement in regulation of sperm functions. With the selective blocking of Nav 1.8 using A-803467, alterations in sperm functions were observed, therefore, we envisaged of investigating the involvement of Nav in regulating sperm function and the mechanism(s) involved in it using veratridine, a selective opener of Nav channels. Forty ejaculates were collected from four Hariana bulls and semen samples were pooled in view of the non-significant variations between the different ejaculates...
November 27, 2017: Theriogenology
https://www.readbyqxmd.com/read/29245901/nav%C3%AE-2-knockdown-improves-cognition-in-app-ps1-mice-by-partially-inhibiting-seizures-and-app-amyloid-processing
#16
Tao Hu, Zhangang Xiao, Rui Mao, Bo Chen, Min-Nan Lu, Jun Tong, Rong Mei, Shan-Shan Li, Zhi-Cheng Xiao, Lian-Feng Zhang, Yan-Bin Xiyang
Voltage-gated sodium channels beta 2 (Navβ2, encoded by SCN2B) is a substrate of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and regulates cell surface expression of channels in neurons. Previous studies reported enhanced Navβ2 processing by BACE1 in Alzheimer's disease (AD) model and patients. We investigated whether changes in Navβ2 expression affect neuronal seizure and amyloid precursor protein (APP) processing in an AD mouse model. Our study used eight-month-old APP/presenilin 1 (PS1) mice and transgenic Navβ2 knockdown [by 61% vs...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29233994/voltage-gated-sodium-channels-assemble-and-gate-as-dimers
#17
Jérôme Clatot, Malcolm Hoshi, Xiaoping Wan, Haiyan Liu, Ankur Jain, Krekwit Shinlapawittayatorn, Céline Marionneau, Eckhard Ficker, Taekjip Ha, Isabelle Deschênes
Fast opening and closing of voltage-gated sodium channels are crucial for proper propagation of the action potential through excitable tissues. Unlike potassium channels, sodium channel α-subunits are believed to form functional monomers. Yet, an increasing body of literature shows inconsistency with the traditional idea of a single α-subunit functioning as a monomer. Here we demonstrate that sodium channel α-subunits not only physically interact with each other but they actually assemble, function and gate as a dimer...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29229553/human-vs-mouse-nociceptors-similarities-and-differences
#18
Charlotte Rostock, Katrin Schrenk-Siemens, Jörg Pohle, Jan Siemens
The somatosensory system allows us to detect a diverse range of physical and chemical stimuli including noxious ones, which can initiate protective reflexes to prevent tissue damage. However, the sensation of pain can -under pathological circumstances- outlive its usefulness and perpetrate ongoing suffering. Rodent model systems have been tremendously useful to help understand basic mechanisms of pain perception. Unfortunately, the translation of this knowledge into novel therapies has been challenging. We have investigated similarities and differences of human and mouse peptidergic (TRKA expressing) nociceptors using dual-color fluorescence in situ hybridization of dorsal root ganglia...
December 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29225974/modulation-effects-of-cordycepin-on-voltage-gated-sodium-channels-in-rat-hippocampal-ca1-pyramidal-neurons-in-the-presence-absence-of-oxygen
#19
Zhi-Bin Liu, Chao Liu, Bin Zeng, Li-Ping Huang, Li-Hua Yao
Our previous study revealed that cordycepin features important neuroprotective effects against hypoxic insult by improvement of neuronal electrophysiological function. Modulation on voltage-gated sodium channel (VGSC) in CA1 neurons is the initial event during hypoxia/ischemia. However, no study comprehensively investigated cordycepin on VGSC. Hence, this study investigated modulation effects of cordycepin on VGSC not only in oxygen physiological conditions but also in acute oxygen deprivation injury conditions...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29218789/precise-localizations-of-voltage-gated-sodium-and-potassium-channels-in-neurons
#20
REVIEW
Hiroaki Misonou
Neurons are extremely large and complex cells, and they regulate membrane potentials in multiple subcellular compartments using a variety of ion channels. Voltage-gated sodium (Nav) and potassium (Kv) channels are crucial in regulating neuronal membrane excitability owing to their diversity in subtypes, biophysical properties, and localizations. In particular, specific localizations of Nav and Kv channels in specific membrane compartments are essential to achieve a precise control of local membrane excitability...
December 8, 2017: Developmental Neurobiology
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