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https://www.readbyqxmd.com/read/29351436/therapeutic-attenuation-of-the-epithelial-sodium-channel-with-a-splunc1-derived-peptide-in-airway-diseases
#1
James F Collawn, Rafal Bartoszewski, Ahmad Lazrak, Sadis Matalon
The airway surface liquid (ASL) coats the lining of the airways and allows for efficient cilial movement and therefore effective mucociliary transport. Cell surface channels regulate the hydration status of the ASL and the two critical channels in the process are the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channel (ENaC). In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) there is loss of CFTR function or compromised CFTR function in chronic bronchitis, respectively...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29347452/incorporating-born-solvation-energy-into-the-three-dimensional-poisson-nernst-planck-model-to-study-ion-selectivity-in-kcsa-k-channels
#2
Xuejiao Liu, Benzhuo Lu
Potassium channels are much more permeable to potassium than sodium ions, although potassium ions are larger and both carry the same positive charge. This puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP) theory of electrodiffusion because the PNP model treats all ions as point charges, does not incorporate ion size information, and therefore cannot discriminate potassium from sodium ions. The PNP model can qualitatively capture some macroscopic properties of certain channel systems such as current-voltage characteristics, conductance rectification, and inverse membrane potential...
December 2017: Physical Review. E
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/29343689/a-novel-%C3%AE-conopeptide-eu1-6-inhibits-n-type-cav2-2-calcium-channels-and-exhibits-potent-analgesic-activity
#4
Zhuguo Liu, Peter Bartels, Mahsa Sadeghi, Tianpeng Du, Qing Dai, Cui Zhu, Shuo Yu, Shuo Wang, Mingxin Dong, Ting Sun, Jiabin Guo, Shuangqing Peng, Ling Jiang, David J Adams, Qiuyun Dai
We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343414/oxaliplatin-and-neuropathy-a-role-for-sodium-channels
#5
EDITORIAL
Susanna B Park, Matthew C Kiernan
No abstract text is available yet for this article.
December 28, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29340775/global-versus-local-mechanisms-of-temperature-sensing-in-ion-channels
#6
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/29339106/safinamide-a-new-hope-for-parkinson-s-disease
#7
REVIEW
Fábio G Teixeira, Miguel F Gago, Paulo Marques, Pedro Silva Moreira, Ricardo Magalhães, Nuno Sousa, António J Salgado
The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson's disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been reported, with safinamide inhibiting glutamate release and sodium/calcium channels, reducing the excitotoxic input to dopaminergic neuronal death...
January 12, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29337552/molecular-dynamics-simulations-of-the-oil-detachment-from-the-hydroxylated-silica-surface-effects-of-surfactants-electrostatic-interactions-and-water-flows-on-the-water-molecular-channel-formation
#8
Jian Tang, Zhou Qu, Jianhui Luo, Lanyan He, Pingmei Wang, Ping Zhang, Xianqiong Tang, Yong Pei, Bin Ding, Baoliang Peng, Yunqing Huang
The detachment process of an oil molecular layer or drop situated above a horizontal substrate was often described by a three-stage process. In this mechanism, the water molecule penetration and diffusion between the oil phase and the solid phase was proposed to be a crucial step to aid in removal of oil drops from solid surfaces. In this work, the detachment process of a two-dimensional alkane molecule layer from a silica surface in aqueous surfactant solutions is studied by means of molecular dynamics (MD) simulations...
January 16, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29337221/venom-characterization-of-the-amazonian-scorpion-tityus-metuendus
#9
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
#10
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/29336990/failure-of-intracardiac-pacing-after-fatal-propafenone-overdose-a-case-report
#11
Ivan Zeljković, Nikola Bulj, Matea Kolačević, Vedran Čabrilo, Diana Delić Brkljačić, Šime Manola
BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic drug, frequently used to manage supraventricular dysrhythmias, especially atrial fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A 68-year-old woman presented with a decreased level of consciousness, hypotension, and electrocardiogram showing QRS widening with atrial asystole and extreme bradycardia < 20 beats/min. After initial stabilization with transcutaneous pacing, laboratory findings detected normal electrolyte ranges and metabolic acidosis, and her medical history revealed availability of propafenone due to paroxysmal atrial fibrillation and depressive syndrome, which led to the suspicion of intoxication...
January 11, 2018: Journal of Emergency Medicine
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
#12
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
#13
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/29331105/dietary-factors-modulate-colonic-tumorigenesis-through-the-interaction-of-gut-microbiota-and-host-chloride-channels
#14
Yong Zhang, Chao Kang, Xiao-Lan Wang, Min Zhou, Meng-Ting Chen, Xiao-Hui Zhu, Kai Liu, Bin Wang, Qian-Yong Zhang, Jun-Dong Zhu, Man-Tian Mi
SCOPE: In recent decades, the association between diet, gut microbiota and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study was to identify the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet or different dose of dihydromyricetin (DMY) interacted with gut microbiota. METHODS AND RESULTS: An AOM/DSS (azoxymethan/dextran sodium sulfate) model was established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis...
January 13, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29329111/severe-peri-ictal-respiratory-dysfunction-is-common-in-dravet-syndrome
#15
YuJaung Kim, Eduardo Bravo, Caitlin K Thirnbeck, Lori A Smith-Mellecker, Se Hee Kim, Brian K Gehlbach, Linda C Laux, Douglas R Nordli Jr, George B Richerson
Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. DS patients have a high risk of sudden unexplained death in epilepsy (SUDEP), believed to be due to cardiac mechanisms. Here we show that DS patients have peri-ictal respiratory dysfunction. One patient who had severe and prolonged postictal hypoventilation later died of SUDEP. Mice with an Scn1aR1407X/+ loss of function mutation died after spontaneous and heat-induced seizures due to central apnea followed by progressive bradycardia...
January 11, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29327365/millimeter-spatial-resolution-in-vivo-sodium-mri-of-the-human-eye-at-7-t-using-a-dedicated-radiofrequency-transceiver-array
#16
Daniel Wenz, Andre Kuehne, Till Huelnhagen, Armin M Nagel, Helmar Waiczies, Oliver Weinberger, Celal Oezerdem, Oliver Stachs, Soenke Langner, Erdmann Seeliger, Bert Flemming, Russell Hodge, Thoralf Niendorf
PURPOSE: The aim of this study was to achieve millimeter spatial resolution sodium in vivo MRI of the human eye at 7 T using a dedicated six-channel transceiver array. We present a detailed description of the radiofrequency coil design, along with electromagnetic field and specific absorption ratio simulations, data validation, and in vivo application. METHODS: Electromagnetic field and specific absorption ratio simulations were performed. Transmit field uniformity was optimized by using a multi-objective genetic algorithm...
January 12, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29327161/effects-of-channel-blocking-on-information-transmission-and-energy-efficiency-in-squid-giant-axons
#17
Yujiang Liu, Yuan Yue, Yuguo Yu, Liwei Liu, Lianchun Yu
Action potentials are the information carriers of neural systems. The generation of action potentials involves the cooperative opening and closing of sodium and potassium channels. This process is metabolically expensive because the ions flowing through open channels need to be restored to maintain concentration gradients of these ions. Toxins like tetraethylammonium can block working ion channels, thus affecting the function and energy cost of neurons. In this paper, by computer simulation of the Hodgkin-Huxley neuron model, we studied the effects of channel blocking with toxins on the information transmission and energy efficiency in squid giant axons...
January 11, 2018: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/29326302/role-of-clc-k-and-barttin-in-low-potassium-induced-sodium-chloride-cotransporter-activation-and-hypertension-in-mouse-kidney
#18
Naohiro Nomura, Wakana Shoda, Yuanlong Wang, Shintaro Mandai, Taisuke Furusho, Daiei Takahashi, Moko Zeniya, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
The sodium-chloride cotransporter (NCC) has been identified as a key molecule regulating potassium balance. The mechanisms of NCC regulation during low extracellular potassium concentrations have been studied in vitro. These studies have shown that hyperpolarization increased chloride efflux, leading to the activation of chloride-sensitive WNK kinases and their downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NCC. However, this mechanism was not studied in vivo Previously, we developed the barttin hypomorphic mouse ( Bsndneo/neo mice), expressing very low levels of barttin and ClC-K channels, because barttin is an essential ß-subunit of ClC-K...
January 11, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29318638/voltage-gated-sodium-channels-nav-igating-the-field-to-determine-their-contribution-to-visceral-nociception
#19
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/29317494/hydrogen-sulfide-inhibits-kir2-and-kir3-channels-by-decreasing-sensitivity-to-the-phospholipid-pip2
#20
Junghoon Ha, Yu Xu, Takeharu Kawano, Tyler Hendon, Lia Baki, Sumanta Garai, Andreas Papapetropoulos, Ganesh Thakur, Leigh D Plant, Diomedes E Logothetis
Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain and other peripheral tissues. Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. The gasotransmitter carbon monoxide has been shown to regulate Kir channel activity by altering channel-PIP2 interactions.  Here, we tested in two cellular models the effects and mechanism of action of another gasotransmitter, hydrogen sulfide (H2S), thought to play a key role in cellular responses under ischemic conditions...
January 9, 2018: Journal of Biological Chemistry
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