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voltage-gated Na channel

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https://www.readbyqxmd.com/read/29160684/improving-the-stability-of-high-performance-multilayer-mos2-field-effect-transistors
#1
Na Liu, Jongyeol Baek, Seung Min Kim, Seongin Hong, Young Ki Hong, Yang Soo Kim, Hyun-Suk Kim, Sunkook Kim, Jozeph Park
In this study, we propose a method for improving the stability of multilayer MoS2 field-effect transistors (FETs) by O2 plasma treatment and Al2O3 passivation sustaining high-performance characteristics of bulk MoS2 FET. The MoS2 FETs were exposed to O2 plasma for 30 s prior to Al2O3 encapsulation, showing a relatively small hysteresis and a high electrical performance. The MoOx layer formed during the plasma treatment was found between MoS2 and the top passivation layer. This MoOx interlayer prevents the generation of excess electron carriers in the channel due to Al2O3 passivation, minimizing the shift of threshold voltage (Vth) and increase of off-current leakage...
November 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#2
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29138928/mechanisms-of-drug-binding-to-voltage-gated-sodium-channels
#3
M E O'Leary, M Chahine
Voltage-gated sodium (Na(+)) channels are expressed in virtually all electrically excitable tissues and are essential for muscle contraction and the conduction of impulses within the peripheral and central nervous systems. Genetic disorders that disrupt the function of these channels produce an array of Na(+) channelopathies resulting in neuronal impairment, chronic pain, neuromuscular pathologies, and cardiac arrhythmias. Because of their importance to the conduction of electrical signals, Na(+) channels are the target of a wide variety of local anesthetic, antiarrhythmic, anticonvulsant, and antidepressant drugs...
November 15, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29138838/effects-of-scn9a-gene-modification-on-na-channel-and-the-expression-of-nerve-growth-factor-in-a-rat-model-of-diarrhea%C3%A2-predominant-irritable-bowel-syndrome
#4
Yong-Yan Cai, Chen Li, Zhi-Xin Yan, Na Ma, Fang-Fang Li
The aim of the present study was to identify whether the sodium voltage-gated channel alpha subunit 9 (SCN9A) gene modification is a potential treatment for diarrhea‑predominant irritable bowel syndrome (D‑IBS), via regulating the Na+ channel and the expression of nerve growth factor (NGF). The recombinant adenovirus vector of the SCN9A gene was established, and rat colon cells were isolated for SCN9A gene modification. All subjects were divided into four groups: i) The SCN9A‑modified (D‑IBS rat model implanted with SCN9A‑modified colon cells), ii) negative control (NC; D‑IBS rat model implanted with colon cells without SCN9A gene modification), iii) blank (D‑IBS rat model without any treatment) and iv) normal (normal rats without any treatment)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29129208/augmented-gene-expression-triggered-by-na-k-atpase-inhibition-role-of-ca-2-i-mediated-and-independent-excitation-transcription-coupling
#5
Larisa V Smolyaninova, Svetlana V Koltsova, Svetlana V Sidorenko, Sergei N Orlov
In rat vascular smooth muscle cells (RVSMC), 3-h Na(+),K(+)-ATPase inhibition by ouabain or in K(+)-free medium resulted in the inversion of the [Na(+)]i/[K(+)]i ratio and elevation up to 7-fold the content of Egr1, Atf3, Nr4a1 and Ptgs2 mRNAs. Ouabain increased the rate of 45Ca(2+) influx by 2-fold that was abolished by L-type voltage-gated Ca(2+) channel blocker nicardipine, but it was resistant to Na(+)/Ca(2+) exchanger inhibitor KB-R7943. To study the role of Ca(2+)-mediated signaling in the expression of Na(+)i/K(+)i-sensitive genes we used intracellular Ca(2+) chelator BAPTA and incubated RVSMC in Ca(2+)-free medium...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29129203/naadp-evoked-ca-2-signals-through-two-pore-channel-1-require-arginine-residues-in-the-first-s4-s5-linker
#6
Sandip Patel, Dev Churamani, Eugen Brailoiu
Two-pore channels (TPCs) are two-domain members of the voltage-gated ion channel superfamily that localize to acidic organelles. Their mechanism of activation (ligands such as NAADP/PI(3,5)P2 versus voltage) and ion selectivity (Ca(2+) versus Na(+)) is debated. Here we report that a cluster of arginine residues in the first domain required for selective voltage-gating of TPC1 map not to the voltage-sensing fourth transmembrane region (S4) but to a cytosolic downstream region (S4-S5 linker). These residues are conserved between TPC isoforms suggesting a generic role in TPC activation...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29114033/na-leak-with-gating-pore-properties-in-hypokalemic-periodic-paralysis-v876e-mutant-muscle-ca-channel
#7
Clarisse Fuster, Jimmy Perrot, Christine Berthier, Vincent Jacquemond, Pierre Charnet, Bruno Allard
Type 1 hypokalemic periodic paralysis (HypoPP1) is a poorly understood genetic neuromuscular disease characterized by episodic attacks of paralysis associated with low blood K(+) The vast majority of HypoPP1 mutations involve the replacement of an arginine by a neutral residue in one of the S4 segments of the α1 subunit of the skeletal muscle voltage-gated Ca(2+) channel, which is thought to generate a pathogenic gating pore current. The V876E HypoPP1 mutation has the peculiarity of being located in the S3 segment of domain III, rather than an S4 segment, raising the question of whether such a mutation induces a gating pore current...
November 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29105388/in-vitro-differentiation-of-neural-like-cells-from-human-embryonic-stem-cells-by-a-combination-of-dorsomorphin-xav939-and-a8301
#8
Zahra Valizadeh-Arshad, Ebrahim Shahbazi, Shiva Hashemizadeh, Azadeh Moradmand, Meyssam Jangkhah, Sahar Kiani
OBJECTIVES: Motor neuron differentiation from human embryonic stem cells (hESCs) is a goal of regenerative medicine to provide cell therapy as treatments for diseases that damage motor neurons. Most protocols lack adequate efficiency in generating functional motor neurons. However, small molecules present a new approach to overcome this challenge. The aim of this research is to replace morphogen factors with a cocktail of efficient, affordable small molecules for effective, low cost motor neuron differentiation...
January 2018: Cell Journal
https://www.readbyqxmd.com/read/29094210/evolutionary-history-of-voltage-gated-sodium-channels
#9
Atsuo Nishino, Yasushi Okamura
Every cell within living organisms actively maintains an intracellular Na(+) concentration that is 10-12 times lower than the extracellular concentration. The cells then utilize this transmembrane Na(+) concentration gradient as a driving force to produce electrical signals, sometimes in the form of action potentials. The protein family comprising voltage-gated sodium channels (NaVs) is essential for such signaling and enables cells to change their status in a regenerative manner and to rapidly communicate with one another...
November 2, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29079724/ca-2-protein-alpha-1d-of-cav1-3-regulates-intracellular-calcium-concentration-and-migration-of-colon-cancer-cells-through-a-non-canonical-activity
#10
Yann Fourbon, Maxime Guéguinou, Romain Félix, Bruno Constantin, Arnaud Uguen, Gaëlle Fromont, Laurie Lajoie, Christophe Magaud, Thierry Lecomte, Emmanuel Chamorey, Aurélien Chatelier, Olivier Mignen, Marie Potier-Cartereau, Aurélie Chantôme, Patrick Bois, Christophe Vandier
It is generally accepted that voltage-gated Ca(2+) channels, CaV, regulate Ca(2+) homeostasis in excitable cells following plasma membrane depolarization. Here, we show that the Ca(2+) protein α1D of CaV1.3 channel is overexpressed in colorectal cancer biopsies compared to normal tissues. Gene silencing experiments targeting α1D reduced the migration and the basal cytosolic Ca(2+) concentration of HCT116 colon cancer cell line and modified the cytosolic Ca(2+) oscillations induced by the sodium/calcium exchanger NCX1/3 working in its reverse mode...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29069799/functional-compatibility-between-purkinje-cell-axon-branches-and-their-target-neurons-in-the-cerebellum
#11
Zhilai Yang, Na Chen, Rongjing Ge, Hao Qian, Jin-Hui Wang
A neuron sprouts an axon, and its branches to innervate many target neurons that are divergent in their functions. In order to efficiently regulate the diversified cells, the axon branches should differentiate functionally to be compatible with their target neurons, i.e., a function compatibility between presynaptic and postsynaptic partners. We have examined this hypothesis by using electrophysiological method in the cerebellum, in which the main axon of Purkinje cell projected to deep nucleus cells and the recurrent axons innervated the adjacent Purkinje cells...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045055/c2-modified-sparteine-derivatives-are-a-new-class-of-potentially-long-acting-sodium-channel-blockers
#12
Vaibhavkumar S Gawali, Svilen Simeonov, Martina Drescher, Thomas Knott, Olaf Scheel, John Kudolo, Hanspeter Kählig, Ulla Hochenegg, Alexander Roller, Hannes Todt, Nuno Maulide
The lupin alkaloid sparteine is a well-known chiral diamine with a range of applications in asymmetric synthesis, as well as a blocker of voltage-gated sodium channels (VGSCs). However, there is only scarce information on the VGSC-blocking activity of sparteine derivatives where the structure of the parent alkaloid is retained. Building on the recent renewed availability of sparteine and derivatives we report herein how modification of sparteine at position 2 produces irreversible blockers of VGSCs. These compounds could be clinically envisaged as long-lasting local anesthetics...
October 17, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29042943/suxiao-jiuxin-pill-protects-cardiomyocytes-against-mitochondrial-injury-and-alters-gene-expression-during-ischemic-injury
#13
Xiaofen Ruan, Tiejun Chen, Xiaolong Wang, Yiping Li
Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting primarily of tetramethylpyrazine and borneol, has been reported to protect against ischemic heart disease. However, the effects of SX on mitochondrial injury and gene expression in various signaling pathways are unclear. The aim of the present study was to investigate the effects of SX on mitochondrial injury and to screen the expression of genes potentially altered by SX using a cell culture model of ischemic injury. Simulated ischemia was established by culturing HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042437/posttranslational-processing-and-membrane-translocation-of-the-yeast-regulatory-mid1-subunit-of-the-cch1-vgcc-nalcn-cation-channel-family
#14
Kazuko Iida, Jinfeng Teng, Toshihiko Cho, Sato Yoshikawa-Kimura, Hidetoshi Iida
Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29032483/regulation-of-cardiac-voltage-gated-sodium-channel-by-kinases-roles-of-protein-kinases-a-and-c
#15
Ademuyiwa S Aromolaran, Mohamed Chahine, Mohamed Boutjdir
In the heart, voltage-gated sodium (Nav) channel (Nav1.5) is defined by its pore-forming α-subunit and its auxiliary β-subunits, both of which are important for its critical contribution to the initiation and maintenance of the cardiac action potential (AP) that underlie normal heart rhythm. The physiological relevance of Nav1.5 is further marked by the fact that inherited or congenital mutations in Nav1.5 channel gene SCN5A lead to altered functional expression (including expression, trafficking, and current density), and are generally manifested in the form of distinct cardiac arrhythmic events, epilepsy, neuropathic pain, migraine, and neuromuscular disorders...
October 15, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28978896/actions-of-propofol-on-neurons-in-the-cerebral-cortex
#16
Masayuki Kobayashi, Yoshiyuki Oi
Propofol is primarily a hypnotic, and is widely used for induction and maintenance of anesthesia, as well as for sedation in various medical procedures. The exact mechanisms of its action are not well understood, although its neural mechanisms have been explored in in vivo and in vitro experiments. Accumulating evidence indicates that one of the major targets of propofol is the cerebral cortex. The principal effect of propofol is considered to be the potentiation of GABAA receptor-mediated inhibitory synaptic currents, but propofol has additional roles in modulating ion channels, including voltage-gated Na(+) channels and several K(+) channels...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/28964110/a-model-of-cardiac-ryanodine-receptor-gating-predicts-experimental-ca-2-dynamics-and-ca-2-triggered-arrhythmia-in-the-long-qt-syndrome
#17
Dan Wilson, Bard Ermentrout, Jan Němec, Guy Salama
Abnormal Ca(2+) handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca(2+) release from Ca(2+)-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca(2+)-channel window current...
September 2017: Chaos
https://www.readbyqxmd.com/read/28963585/effects-of-eugenol-on-respiratory-burst-generation-in-newborn-rat-brainstem-spinal-cord-preparations
#18
Sayumi Kotani, Saki Irie, Masahiko Izumizaki, Hiroshi Onimaru
Eugenol is contained in several plants including clove and is used as an analgesic drug. In the peripheral and central nervous systems, this compound modulates neuronal activity through action on voltage-gated ionic channels and/or transient receptor potential channels. However, it is unknown whether eugenol exerts any effects on the respiratory center neurons in the medulla. We examined the effects of eugenol on respiratory rhythm generation in the brainstem-spinal cord preparation from newborn rat (P0-P3)...
September 29, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28943231/active-mechanisms-of-vibration-encoding-and-frequency-filtering-in-central-mechanosensory-neurons
#19
Anthony W Azevedo, Rachel I Wilson
To better understand biophysical mechanisms of mechanosensory processing, we investigated two cell types in the Drosophila brain (A2 and B1 cells) that are postsynaptic to antennal vibration receptors. A2 cells receive excitatory synaptic currents in response to both directions of movement: thus, twice per vibration cycle. The membrane acts as a low-pass filter, so that voltage and spiking mainly track the vibration envelope rather than individual cycles. By contrast, B1 cells are excited by only forward or backward movement, meaning they are sensitive to vibration phase...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/28939972/effects-of-benzothiazolamines-on-voltage-gated-sodium-channels
#20
Alessandro Farinato, Concetta Altamura, Jean-François Desaphy
Benzothiazole is a versatile fused heterocycle that aroused much interest in drug discovery as anticonvulsant, neuroprotective, analgesic, anti-inflammatory, antimicrobial, and anticancer. Two benzothiazolamines, riluzole and lubeluzole, are known blockers of voltage-gated sodium (Nav) channels. Riluzole is clinically used as a neuroprotectant in amyotrophic lateral sclerosis. Inhibition of Nav channels by riluzole is voltage-dependent due to preferential binding to inactivated sodium channels. Yet the drug exerts little use-dependent block, probably because it lacks protonable amine...
September 23, 2017: Handbook of Experimental Pharmacology
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