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voltage-gated Na channel

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https://www.readbyqxmd.com/read/29333676/ether-%C3%A3-go-go-k-channels-effective-modulators-of-neuronal-excitability
#1
Christiane K Bauer, Jürgen R Schwarz
Mammalian EAG (ether-à-go-go) channels are voltage-gated K+ channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation...
January 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29333591/differential-inhibition-of-nav1-7-and-neuropathic-pain-by-hybridoma-produced-and-recombinant-monoclonal-antibodies-that-target-nav1-7-differential-activities-of-nav1-7-targeting-monoclonal-antibodies
#2
Sangsu Bang, Jiho Yoo, Xingrui Gong, Di Liu, Qingjian Han, Xin Luo, Wonseok Chang, Gang Chen, Sang-Taek Im, Yong Ho Kim, Judith A Strong, Ma-Zhong Zhang, Jun-Ming Zhang, Seok-Yong Lee, Ru-Rong Ji
The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1...
January 15, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29330525/distinct-modulation-of-inactivation-by-a-residue-in-the-pore-domain-of-voltage-gated-na-channels-mechanistic-insights-from-recent-crystal-structures
#3
Rene Cervenka, Peter Lukacs, Vaibhavkumar S Gawali, Song Ke, Xaver Koenig, Lena Rubi, Touran Zarrabi, Karlheinz Hilber, Walter Sandtner, Anna Stary-Weinzinger, Hannes Todt
Inactivation of voltage-gated Na+ channels (VGSC) is essential for the regulation of cellular excitability. The molecular rearrangement underlying inactivation is thought to involve the intracellular linker between domains III and IV serving as inactivation lid, the receptor for the lid (domain III S4-S5 linker) and the pore-lining S6 segements. To better understand the role of the domain IV S6 segment in inactivation we performed a cysteine scanning mutagenesis of this region in rNav 1.4 channels and screened the constructs for perturbations in the voltage-dependence of steady state inactivation...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29222130/stargazin-and-cornichon-3-relieve-polyamine-block-of-ampa-receptors-by-enhancing-blocker-permeation
#4
Patricia M G E Brown, Hugo McGuire, Derek Bowie
Most ligand- and voltage-gated ion channels assemble as signaling complexes consisting of pore-forming and auxiliary subunits. In the mammalian brain, AMPA-type ionotropic glutamate receptors (AMPARs) coassemble with several families of auxiliary subunits that regulate channel gating as well as ion channel block and permeation. Previous work has shown that auxiliary proteins stargazin (or γ2) and cornichon-3 (CNIH-3) attenuate the cytoplasmic polyamine channel block of AMPARs, although the underlying mechanism has yet to be established...
December 8, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29190805/single-molecule-study-of-full-length-nachbac-by-planar-lipid-bilayer-recording
#5
Andrew Jo, Hiofan Hoi, Hang Zhou, Manisha Gupta, Carlo D Montemagno
Planar lipid bilayer device, alternatively known as BLM, is a powerful tool to study functional properties of conducting membrane proteins such as ion channels and porins. In this work, we used BLM to study the prokaryotic voltage-gated sodium channel (Nav) NaChBac in a well-defined membrane environment. Navs are an essential component for the generation and propagation of electric signals in excitable cells. The successes in the biochemical, biophysical and crystallographic studies on prokaryotic Navs in recent years has greatly promoted the understanding of the molecular mechanism that underlies these proteins and their eukaryotic counterparts...
2017: PloS One
https://www.readbyqxmd.com/read/29188487/sodium-metabisulfite-effects-on-ionic-currents-and-excitotoxicity
#6
Ming-Chi Lai, Te-Yu Hung, Kao-Min Lin, Pi-Shan Sung, Shyh-Jong Wu, Chih-Sheng Yang, Yi-Jen Wu, Jing-Jane Tsai, Sheng-Nan Wu, Chin-Wei Huang
How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment...
November 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29185841/inhibitory-effect-of-amitriptyline-on-the-impulse-activity-of-cold-thermoreceptor-terminals-of-intact-and-tear-deficient-guinea-pig-corneas
#7
Takayoshi Masuoka, Juana Gallar, Carlos Belmonte
PURPOSE: Chronic dryness of the ocular surface evokes sensitization of corneal cold-sensitive neurons through an increase of sodium currents and a decrease of potassium currents, leading to the unpleasant dryness and pain sensations typical of dry eye disease. Here, we explored the effects of amitriptyline, a voltage-gated Na+ channel blocker used for the treatment of depression and chronic pain, on nerve terminal impulse (NTI) activity of cold-sensitive nerve terminals recorded in intact and tear-deficient guinea pig corneas...
November 29, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29167113/irritable-bowel-syndrome-ibs-patients-have-scn5a-channelopathies-that-lead-to-decreased-nav1-5-current-and-mechanosensitivity
#8
Peter R Strege, Amelia Mazzone, Cheryl E Bernard, Leila Neshatian, Simon J Gibbons, Yuri A Saito, David J Tester, Melissa L Calvert, Emeran A Mayer, Lin Chang, Michael J Ackerman, Arthur Beyder, Gianrico Farrugia
The SCN5A-encoded voltage-gated mechanosensitive sodium (Na(+)) channel NaV1.5 is expressed in human GI smooth muscle cells and interstitial cells of Cajal. NaV1.5 contributes to smooth muscle electrical slow waves and mechanical sensitivity. In predominately Caucasian IBS patient cohorts, 2-3% have SCN5A missense mutations which alter NaV1.5 function and may contribute to IBS pathophysiology. In this study examined a racially and ethnically diverse cohort of IBS patients for SCN5A missense mutations, and compared them to IBS negative controls, and determined the resulting NaV1...
November 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29160684/improving-the-stability-of-high-performance-multilayer-mos2-field-effect-transistors
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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