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Voltage-gated sodium channel

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https://www.readbyqxmd.com/read/28727929/na-h-exchanger-and-proton-channel-in-heart-failure-associated-with-becker-and-duchenne-muscular-dystrophy
#1
Ghassan Bkaily, Danielle Jacques
Cardiomyopathy is found in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies which are linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects are not limited to DMD but are also present in mild BMD. The hereditary cardiomyopathic hamster of the UM-X7.1 strain is a particular experimental model of heart failure (HF) leading to early death in muscular dystrophy (dystrophin deficiency and sarcoglycan mutation) and heart disease (δ-sarcoglycan deficiency and dystrophin mutation) in human DMD...
July 20, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28725028/detection-and-quantitation-of-copy-number-variation-in-the-voltage-gated-sodium-channel-gene-of-the-mosquito-culex-quinquefasciatus
#2
Walter Fabricio Silva Martins, Krishanthi Subramaniam, Keith Steen, Henry Mawejje, Triantafillos Liloglou, Martin James Donnelly, Craig Stephen Wilding
Insecticide resistance is typically associated with alterations to the insecticidal target-site or with gene expression variation at loci involved in insecticide detoxification. In some species copy number variation (CNV) of target site loci (e.g. the Ace-1 target site of carbamate insecticides) or detoxification genes has been implicated in the resistance phenotype. We show that field-collected Ugandan Culex quinquefasciatus display CNV for the voltage-gated sodium channel gene (Vgsc), target-site of pyrethroid and organochlorine insecticides...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718687/do-sodium-channel-proteolytic-fragments-regulate-sodium-channel-expression
#3
Donatus O Onwuli, Laia Yañez-Bisbe, Mellina Pinsach-Abuin, Anna Tarradas, Ramon Brugada, John Greenman, Sara Pagans, Pedro Beltran-Alvarez
The cardiac voltage-gated sodium channel (gene: SCN5A, protein: NaV1.5) is responsible for the sodium current that initiates the cardiomyocyte action potential. Research into the mechanisms of SCN5A gene expression has gained momentum over the last few years. We have recently described the transcriptional regulation of SCN5A by GATA4 transcription factor. In this addendum to our study, we report our observations that 1) the linker between domains I and II (LDI-DII) of NaV1.5 contains a nuclear localisation signal (residues 474-481) that is necessary to localise LDI-DII into the nucleus, and 2) nuclear LDI-DII activates the SCN5A promoter in gene reporter assays using cardiac-like H9c2 cells...
July 18, 2017: Channels
https://www.readbyqxmd.com/read/28712915/comparative-analyses-and-implications-for-antivenom-serotherapy-of-four-moroccan-scorpion-buthus-occitanus-venoms-subspecies-tunetanus-paris-malhommei-and-mardochei
#4
Bruna Luiza Emerich, Maria Elena De Lima, Marie-France Martin-Eauclaire, Pierre E Bougis
Temporary passive immunity such as serotherapy against venoms requires the full knowledge of all venom's components. Here, four venoms from Moroccan common yellow scorpions belonging to Buthus occitanus, subspecies tunetanus, paris, malhommei, and mardochei, all collected in four different restricted areas, were analysed in deep. They were fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC) and their molecular masse profile determined by off-line MALDI-TOF mass spectrometry. Characterisation of their main components was achieved by enzyme-linked immunosorbent assay (ELISA) using specific antisera against the major lethal scorpion toxins identified so far, i...
July 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28711494/development-of-membrane-ion-channels-during-neural-differentiation-from-human-embryonic-stem-cells
#5
Sara Mirsadeghi, Ebrahim Shahbazi, Katayoun Hemmesi, Shiva Nemati, Hossein Baharvand, Javad Mirnajafi-Zadeh, Sahar Kiani
OBJECTIVE: For human embryonic stem cells (hESCs) to differentiate into neurons, enormous changes has to occur leading to trigger action potential and neurotransmitter release. We attempt to determine the changes in expression of voltage gated channels (VGCs) and their electrophysiological properties during neural differentiation. MATERIALS AND METHODS: The relative expressions of α-subunit of voltage gated potassium, sodium and calcium channels were characterized by qRT-PCR technique...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710444/ergodicity-breaking-on-the-neuronal-surface-emerges-from-random-switching-between-diffusive-states
#6
Aleksander Weron, Krzysztof Burnecki, Elizabeth J Akin, Laura Solé, Michał Balcerek, Michael M Tamkun, Diego Krapf
Stochastic motion on the surface of living cells is critical to promote molecular encounters that are necessary for multiple cellular processes. Often the complexity of the cell membranes leads to anomalous diffusion, which under certain conditions it is accompanied by non-ergodic dynamics. Here, we unravel two manifestations of ergodicity breaking in the dynamics of membrane proteins in the somatic surface of hippocampal neurons. Three different tagged molecules are studied on the surface of the soma: the voltage-gated potassium and sodium channels Kv1...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701749/calcium-activated-sk-channels-control-firing-regularity-by-modulating-sodium-channel-availability-in-midbrain-dopamine-neurons
#7
Rajeshwari Iyer, Mark A Ungless, Aldo A Faisal
Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area regulate behaviours such as reward-related learning, and motor control. Dysfunction of these neurons is implicated in Schizophrenia, addiction to drugs, and Parkinson's disease. While some dopamine neurons fire single spikes at regular intervals, others fire irregular single spikes interspersed with bursts. Pharmacological inhibition of calcium-activated potassium (SK) channels increases the variability in their firing pattern, sometimes also increasing the number of spikes fired in bursts, indicating that SK channels play an important role in maintaining dopamine neuron firing regularity and burst firing...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700368/regional-anesthesia-and-analgesia-in-cancer-care-is-it-time-to-break-the-bad-news
#8
Mir W Sekandarzad, André A J van Zundert, Chris W Doornebal, Markus W Hollmann
PURPOSE OF REVIEW: There is ongoing controversy regarding the tumor-protective effects of regional anesthesia in patients undergoing cancer surgery. Evidence of up-to-date systematic reviews will be presented alongside recent updates on the effects of opioids and local anesthetics. RECENT FINDINGS: In recent years, the literature regarding the effects of regional anesthesia techniques on cancer recurrence has raised many unanswered questions. Ongoing randomized controlled trials may not be able to shed light on the controversial discussion regarding the tumor protective effects of regional anesthesia because the expected effect size and event rate in those studies may be overstated...
July 11, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28698102/neonatal-nav1-5-protein-expression-in-normal-adult-human-tissues-and-breast-cancer
#9
Rezan Fahrioglu Yamaci, Scott P Fraser, Esra Battaloglu, Handan Kaya, Kamil Erguler, Christopher S Foster, Mustafa B A Djamgoz
Expression of the neonatal splice variant of the voltage-gated sodium channel α-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel(®)in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28695248/divergent-effects-of-anesthetics-on-lipid-bilayer-properties-and-sodium-channel-function
#10
REVIEW
Karl F Herold, Olaf S Andersen, Hugh C Hemmings
General anesthetics revolutionized medicine by allowing surgeons to perform more complex and much longer procedures. This widely used class of drugs is essential to patient care, yet their exact molecular mechanism(s) are incompletely understood. One early hypothesis over a century ago proposed that nonspecific interactions of anesthetics with the lipid bilayer lead to changes in neuronal function via effects on membrane properties. This model was supported by the Meyer-Overton correlation between anesthetic potency and lipid solubility and despite more recent evidence for specific protein targets, in particular ion-channels, lipid bilayer-mediated effects of anesthetics is still under debate...
July 10, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28686619/rare-variants-of-small-effect-size-in-neuronal-excitability-genes-influence-clinical-outcome-in-japanese-cases-of-scn1a-truncation-positive-dravet-syndrome
#11
Michael F Hammer, Atsushi Ishii, Laurel Johnstone, Alexander Tchourbanov, Branden Lau, Ryan Sprissler, Brian Hallmark, Miao Zhang, Jin Zhou, Joseph Watkins, Shinichi Hirose
Dravet syndrome (DS) is a rare, devastating form of childhood epilepsy that is often associated with mutations in the voltage-gated sodium channel gene, SCN1A. There is considerable variability in expressivity within families, as well as among individuals carrying the same primary mutation, suggesting that clinical outcome is modulated by variants at other genes. To identify modifier gene variants that contribute to clinical outcome, we sequenced the exomes of 22 individuals at both ends of a phenotype distribution (i...
2017: PloS One
https://www.readbyqxmd.com/read/28683073/high-throughput-electrophysiological-assays-for-voltage-gated-ion-channels-using-syncropatch-768pe
#12
Tianbo Li, Gang Lu, Eugene Y Chiang, Tania Chernov-Rogan, Jane L Grogan, Jun Chen
Ion channels regulate a variety of physiological processes and represent an important class of drug target. Among the many methods of studying ion channel function, patch clamp electrophysiology is considered the gold standard by providing the ultimate precision and flexibility. However, its utility in ion channel drug discovery is impeded by low throughput. Additionally, characterization of endogenous ion channels in primary cells remains technical challenging. In recent years, many automated patch clamp (APC) platforms have been developed to overcome these challenges, albeit with varying throughput, data quality and success rate...
2017: PloS One
https://www.readbyqxmd.com/read/28680914/antiepileptic-drug-therapy-in-patients-with-autoimmune-epilepsy
#13
Anteneh M Feyissa, A Sebastian López Chiriboga, Jeffrey W Britton
OBJECTIVE: We aimed to report the pattern of usage and efficacy of antiepileptic drugs (AEDs) in patients with autoimmune epilepsy (AE). METHODS: We retrospectively studied the Mayo Clinic's electronic medical record of patients with AE in which seizures were the main presenting feature. Clinical data, including demographics, seizure characteristics, type of AED and immunotherapy used, presence of neural antibody, and treatment outcomes, were reviewed. RESULTS: The medical records of 252 adult patients diagnosed with autoimmune encephalitis and paraneoplastic disorders were reviewed...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28679467/effects-of-a-novel-sodium-channel-blocker-gsk2339345-in-patients-with-refractory-chronic-cough%C3%A2
#14
Jaclyn A Smith, Lorcan P A McGarvey, Huda Badri, Imran Satia, Francis Warren, Sarah Siederer, Lia Liefaard, Robert D Murdoch, Kathryn Povey, Joanna Marks-Konczalik
OBJECTIVE: Voltage-gated sodium channels (VGSC) are important in the initiation and propagation of action potentials in afferent sensory nerve fibers responsible for evoking cough. This study investigated the efficacy of GSK2339345, a VGSC inhibitor, in the treatment of refractory chronic cough (RCC). METHODS: A three-part randomized, double-blind, placebo-controlled, cross-over study was conducted in the UK. In part A, patients with RCC received two inhaled doses of either GSK2339345 or placebo, 4 hours apart during three study periods...
July 6, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28676574/aberrant-sodium-channel-currents-and-hyperexcitability-of-medial-entorhinal-cortex-neurons-in-a-mouse-model-of-scn8a-encephalopathy
#15
Matteo Ottolini, Bryan S Barker, Ronald P Gaykema, Miriam H Meisler, Manoj K Patel
SCN8A encephalopathy, or early infantile epileptic encephalopathy 13 (EIEE13), is caused predominantly by de novo gain-of-function mutations in the voltage-gated sodium (Na) channel Nav1.6. Affected individuals suffer from refractory seizures, developmental delay, cognitive disability and elevated risk of sudden unexpected death in epilepsy (SUDEP). A knock-in mouse model carrying the patient mutation p.Asn1768Asp (N1768D) reproduces many features of the disorder including spontaneous seizures and SUDEP. We used the mouse model to examine the effects of the mutation on layer II stellate neurons of the medial entorhinal cortex (mEC), which transmit excitatory input to the hippocampus...
July 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28676440/severe-bone-loss-and-multiple-fractures-in-scn8a-related-epileptic-encephalopathy
#16
Tim Rolvien, Sebastian Butscheidt, Anke Jeschke, Axel Neu, Jonas Denecke, Christian Kubisch, Miriam H Meisler, Klaus Pueschel, Florian Barvencik, Timur Yorgan, Ralf Oheim, Thorsten Schinke, Michael Amling
Mutations in the SCN8A gene encoding the neuronal voltage-gated sodium channel Nav1.6 are known to be associated with epileptic encephalopathy type 13. We identified a novel de novo SCN8A mutation (p.Phe360Ala, c.1078_1079delTTinsGC, Exon 9) in a 6-year-old girl with epileptic encephalopathy accompanied by severe juvenile osteoporosis and multiple skeletal fractures, similar to three previous case reports. Skeletal assessment using dual energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) and serum analyses revealed a combined trabecular and cortical bone loss syndrome with elevated bone resorption...
July 1, 2017: Bone
https://www.readbyqxmd.com/read/28667054/analysis-of-decreases-in-systemic-arterial-pressure-and-heart-rate-in-response-to-the-hydrogen-sulfide-donor-sodium-sulfide
#17
Kevin W Swan, Bryant Minkyu Song, Allen L Chen, Travis J Chen, Ryan A Chan, Bradley T Guidry, Prasad V G Katakam, Edmund K Kerut, Thomas D Giles, Philip Kadowitz
The actions of hydrogen sulfide (H2S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H2S are unclear in the anesthetized rat. The objective of the current study is to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous (iv) administration of the H2S donor sodium sulfide (Na2S) in the anesthetized Sprague-Dawley (SD) rat decreased MAP and HR and produced changes in respiratory function...
June 30, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28664031/large-scale-structural-alteration-of-brain-in-epileptic-children-with-scn1a-mutation
#18
Yun-Jeong Lee, Mi-Sun Yum, Min-Jee Kim, Woo-Hyun Shim, Hee Mang Yoon, Il Han Yoo, Jiwon Lee, Byung Chan Lim, Ki Joong Kim, Tae-Sung Ko
OBJECTIVE: Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS +) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic children with SCN1A mutation compared to healthy control subjects...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28658526/reverse-pharmacogenomics-carbamazepine-normalizes-activation-and-attenuates-thermal-induced-hyperexcitability-of-sensory-neurons-due-to-nav1-7-mutation-i234t
#19
Yang Yang, Talia Adi, Philip Effraim, Lubin Chen, Sulayman D Dib-Hajj, Stephen G Waxman
BACKGROUND AND PURPOSE: Pharmacotherapy for pain currently involves trial-and-error. A previous study on inherited erythromelalgia (a genetic model of neuropathic pain due to mutations in voltage-gated sodium channel Nav1.7) used genomics, structural modeling, biophysical and pharmacological analyses to guide pharmacotherapy, and showed that carbamazepine normalizes voltage-dependence of activation of the Nav1.7-S241T mutant channel, reducing pain in patients carrying this mutation. However, whether this approach is applicable to other Nav mutations is still unknown...
June 28, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28655765/parallel-homodimer-structures-of-the-extracellular-domains-of-the-voltage-gated-sodium-channel-%C3%AE-4-subunit-explain-its-role-in-cell-cell-adhesion
#20
Hideaki Shimizu, Asako Tosaki, Noboru Ohsawa, Yoshiko Ishizuka-Katsura, Shisako Shoji, Haruko Miyazaki, Fumitaka Oyama, Takaho Terada, Mikako Shirouzu, Shun-Ichi Sekine, Nobuyuki Nukina, Shigeyuki Yokoyama
Voltage-gated sodium channels (VGSCs) are transmembrane proteins required for the generation of action potentials in excitable cells and essential for propagating electrical impulses along nerve cells. VGSCs are complexes of a pore-forming α subunit and auxiliary β subunits, designated as β1/β1B-β4 (encoded by SCN1B-4B, respectively), which also function in cell-cell adhesion. We previously reported the structural basis for the trans homophilic interaction of the β4 subunit, which contributes to its adhesive function...
June 27, 2017: Journal of Biological Chemistry
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