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https://www.readbyqxmd.com/read/27903401/-impact-of-neuronal-sodium-channel-nav-1-8-on-cardiac-function-and-cardiovascular-diseases
#1
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No abstract text is available yet for this article.
November 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/27896920/fusion-of-ssm6a-with-a-protein-scaffold-retains-selectivity-on-nav-1-7-and-improves-its-therapeutic-potential-against-chronic-pain
#2
Chuan Wang, Bin Shan, Qiong Wang, Qunyuan Xu, Hailin Zhang, Huimeng Lei
Voltage gated sodium channel NaV 1.7 serves an attractive target for chronic pain treatment. Several venom peptides were found to selectively inhibit NaV 1.7 but with intrinsic problems. Among them, Ssm6a, a recently discovered centipede venom peptide, shows the greatest selectivity against NaV 1.7, but dissociates from the target too fast and loses bioactivity in synthetic forms. As a disulfide-rich venom peptide, it is difficult to optimize Ssm6a by artificial mutagenesis and produce the peptide with common industrial manufacturing methods...
November 29, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27896032/gene-expression-profile-of-sodium-channel-subunits-in-the-anterior-cingulate-cortex-during-experimental-paclitaxel-induced-neuropathic-pain-in-mice
#3
Willias Masocha
Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal pathophysiology is not fully understood. Dysregulation of sodium channel expression, studied mainly in the periphery and spinal cord level, contributes to the pathogenesis of neuropathic pain. We examined gene expression of sodium channel (Nav) subunits by real time polymerase chain reaction (PCR) in the anterior cingulate cortex (ACC) at day 7 post first administration of paclitaxel, when mice had developed paclitaxel-induced thermal hyperalgesia...
2016: PeerJ
https://www.readbyqxmd.com/read/27886338/frequency-of-the-val1016ile-mutation-on-the-kdr-gene-in-aedes-aegypti-diptera-culicidae-in-south-brazil
#4
M L Collet, C Frizzo, E Orlandin, L D P Rona, J C Nascimento, M A E Montano, G A Müller, G Wagner
Recently, the number of Aedes aegypti foci has increased in west of Santa Catarina, south Brazil, which has increased concern regarding mosquito-borne disease outbreaks such as dengue fever, Zika virus, and chikungunya. Therefore, it is important to monitor genetic resistance to insecticides through "knockdown resistance". Homozygosity (Ile/Ile) at position 1016 in the coding region of a voltage-dependent sodium channel gene (Nav) may induce resistance to pyrethroid insecticides. We evaluated the frequency of these alleles in A...
November 21, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27856903/asymmetric-synthesis-of-batrachotoxin-enantiomeric-toxins-show-functional-divergence-against-nav
#5
Matthew M Logan, Tatsuya Toma, Rhiannon Thomas-Tran, J Du Bois
The steroidal neurotoxin (-)-batrachotoxin functions as a potent agonist of voltage-gated sodium ion channels (NaVs). Here we report concise asymmetric syntheses of the natural (-) and non-natural (+) antipodes of batrachotoxin, as well both enantiomers of a C-20 benzoate-modified derivative. Electrophysiological characterization of these molecules against NaV subtypes establishes the non-natural toxin enantiomer as a reversible antagonist of channel function, markedly different in activity from (-)-batrachotoxin...
November 18, 2016: Science
https://www.readbyqxmd.com/read/27856739/fluorine-19-nmr-and-computational-quantification-of-isoflurane-binding-to-the-voltage-gated-sodium-channel-nachbac
#6
Monica N Kinde, Vasyl Bondarenko, Daniele Granata, Weiming Bu, Kimberly C Grasty, Patrick J Loll, Vincenzo Carnevale, Michael L Klein, Roderic G Eckenhoff, Pei Tang, Yan Xu
Voltage-gated sodium channels (NaV) play an important role in general anesthesia. Electrophysiology measurements suggest that volatile anesthetics such as isoflurane inhibit NaV by stabilizing the inactivated state or altering the inactivation kinetics. Recent computational studies suggested the existence of multiple isoflurane binding sites in NaV, but experimental binding data are lacking. Here we use site-directed placement of (19)F probes in NMR experiments to quantify isoflurane binding to the bacterial voltage-gated sodium channel NaChBac...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27844061/lithium-responsive-seizure-like-hyperexcitability-is-caused-by-a-mutation-in-the-drosophila-voltage-gated-sodium-channel-gene-paralytic
#7
Garrett A Kaas, Junko Kasuya, Patrick Lansdon, Atsushi Ueda, Atulya Iyengar, Chun-Fang Wu, Toshihiro Kitamoto
Shudderer (Shu) is an X-linked dominant mutation in Drosophila melanogaster identified more than 40 years ago. A previous study showed that Shu caused spontaneous tremors and defects in reactive climbing behavior, and that these phenotypes were significantly suppressed when mutants were fed food containing lithium, a mood stabilizer used in the treatment of bipolar disorder (Williamson, 1982). This unique observation suggested that the Shu mutation affects genes involved in lithium-responsive neurobiological processes...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27832602/activity-dependent-formation-and-location-of-voltage-gated-sodium-channel-clusters-at-a-cns-nerve-terminal-during-postnatal-development
#8
Jie Xu, Emmanuelle Berret, Jun Hee Kim
In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Nav) channels clustered at nodes of Ranvier. Changes in Nav channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. Here, we studied the activity-dependent formation of Nav channel clusters before and after hearing onset at P12 in the rat and mouse auditory brainstem. In rats, the Nav channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Nav channel cluster at the nodes was present before hearing onset...
November 9, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27830185/fhf1-fgf12-epileptic-encephalopathy
#9
Sameer Al-Mehmadi, Miranda Splitt, Venkateswaran Ramesh, Suzanne DeBrosse, Kimberly Dessoffy, Fan Xia, Yaping Yang, Jill A Rosenfeld, Patrick Cossette, Jacques L Michaud, Fadi F Hamdan, Philippe M Campeau, Berge A Minassian
Voltage-gated sodium channels (Navs) are mainstays of neuronal function, and mutations in the genes encoding CNS Navs (Nav1.1 [SCN1A], Nav1.2 [SCN2A], Nav1.3 [SCN3A], and Nav1.6 [SCN8A]) are causes of some of the most common and severe genetic epilepsies and epileptic encephalopathies (EE).(1) Fibroblast-growth-factor homologous factors (FHFs) compose a family of 4 proteins that interact with the C-terminal tails of Navs to modulate the channels' fast, and long-term, inactivations.(2)FHF2 mutation is a rare cause of generalized epilepsy with febrile seizures plus (GEFS+)...
December 2016: Neurology. Genetics
https://www.readbyqxmd.com/read/27816572/characterization-of-an-insect-heterodimeric-voltage-gated-sodium-channel-with-unique-alternative-splicing-mode
#10
Xuan-Zhao Jiang, Yu-Xia Pei, Wei Lei, Ke-Yi Wang, Feng Shang, Hong-Bo Jiang, Jin-Jun Wang
Recent discovery of the heterodimeric voltage-gated sodium channels (Nav) in two aphid species, Acyrthosiphon pisum and Myzus persicae, aroused interest in exploring whether this kind of channel is conserved for aphids. Herewith, we aim to provide evidence for the conservation of heterodimeric Navs in aphids and investigate whether they have unique splicing patterns. We found that the only identifiable Nav from Toxoptera citricida consisted of two subunits, forming a heterodimeric Nav, which carried an atypical "DENS" ion selectivity filter and a conventional "MFM" inactivation gate, confirming the heterodimeric Navs' conservation within aphids...
November 2, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27801785/novel-conopeptides-of-largely-unexplored-indo-pacific-conus-sp
#11
Eline K M Lebbe, Maarten G K Ghequire, Steve Peigneur, Bea G Mille, Prabha Devi, Samuthirapandian Ravichandran, Etienne Waelkens, Lisette D'Souza, René De Mot, Jan Tytgat
Cone snails are predatory creatures using venom as a weapon for prey capture and defense. Since this venom is neurotoxic, the venom gland is considered as an enormous collection of pharmacologically interesting compounds having a broad spectrum of targets. As such, cone snail peptides represent an interesting treasure for drug development. Here, we report five novel peptides isolated from the venom of Conus longurionis, Conus asiaticus and Conus australis. Lo6/7a and Lo6/7b were retrieved from C. longurionis and have a cysteine framework VI/VII...
October 27, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27781142/pathological-nociceptors-in-two-patients-with-erythromelalgia-like-symptoms-and-rare-genetic-nav-1-9-variants
#12
Inge P Kleggetveit, Roland Schmidt, Barbara Namer, Hugh Salter, Tormod Helås, Martin Schmelz, Ellen Jørum
INTRODUCTION: The sodium channel Nav 1.9 is expressed in peripheral nociceptors and has recently been linked to human pain conditions, but the exact role of Nav 1.9 for human nociceptor excitability is still unclear. METHODS: C-nociceptors from two patients with late onset of erythromelalgia-like pain, signs of small fiber neuropathy, and rare genetic variants of Nav 1.9 (N1169S, I1293V) were assessed by microneurography. RESULTS: Compared with patients with comparable pain phenotypes (erythromelalgia-like pain without Nav-mutations and painful polyneuropathy), there was a tendency toward more activity-dependent slowing of conduction velocity in mechanoinsensitive C-nociceptors...
October 2016: Brain and Behavior
https://www.readbyqxmd.com/read/27763551/the-snake-with-the-scorpion-s-sting-novel-three-finger-toxin-sodium-channel-activators-from-the-venom-of-the-long-glanded-blue-coral-snake-calliophis-bivirgatus
#13
Daryl C Yang, Jennifer R Deuis, Daniel Dashevsky, James Dobson, Timothy N W Jackson, Andreas Brust, Bing Xie, Ivan Koludarov, Jordan Debono, Iwan Hendrikx, Wayne C Hodgson, Peter Josh, Amanda Nouwens, Gregory J Baillie, Timothy J C Bruxner, Paul F Alewood, Kelvin Kok Peng Lim, Nathaniel Frank, Irina Vetter, Bryan G Fry
Millions of years of evolution have fine-tuned the ability of venom peptides to rapidly incapacitate both prey and potential predators. Toxicofera reptiles are characterized by serous-secreting mandibular or maxillary glands with heightened levels of protein expression. These glands are the core anatomical components of the toxicoferan venom system, which exists in myriad points along an evolutionary continuum. Neofunctionalisation of toxins is facilitated by positive selection at functional hotspots on the ancestral protein and venom proteins have undergone dynamic diversification in helodermatid and varanid lizards as well as advanced snakes...
October 18, 2016: Toxins
https://www.readbyqxmd.com/read/27714768/effects-of-s906t-polymorphism-on-the-severity-of-a-novel-borderline-mutation-i692m-in-nav-1-4-cause-periodic-paralysis
#14
Chunxiang Fan, Ninghui Mao, Frank Lehmann-Horn, Jan Bürmann, Karin Jurkat-Rott
Hyperkalemic periodic paralysis (HyperPP) is a dominantly inherited muscle disease caused by mutations in SCN4A gene encoding skeletal muscle voltage gated Nav 1.4 channels. We identified a novel Nav 1.4 mutation I692M in 14 families out of the 104 genetically identified HyperPP families in the Neuromuscular Centre Ulm and is therefore as frequent as I693T (13 families out of 14 HyperPP families) in Germany. Surprisingly, in 13 families, a known polymorphism S906T was also present. It was on the affected allele in at least 10 families compatible with a possible founder effect in central Europe...
October 6, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27690427/discovery-of-dihydrobenzoxazepinone-gs-6615-late-sodium-current-inhibitor-late-inai-a-phase-ii-agent-with-demonstrated-preclinical-anti-ischemic-and-antiarrhythmic-properties
#15
Jeff A Zablocki, Elfatih Elzein, Xiaofen Li, Dmitry O Koltun, Eric Q Parkhill, Tetsuya Kobayashi, Ruben Martinez, Britton Corkey, Haibo Jiang, Thao Perry, Rao Kalla, Gregory T Notte, Oliver Saunders, Michael Graupe, Yafan Lu, Chandru Venkataramani, Juan Guerrero, Jason Perry, Mark Osier, Robert Strickley, Gongxin Liu, Wei-Qun Wang, Lufei Hu, Xiao-Jun Li, Nesrine El-Bizri, Ryoko Hirakawa, Kris Kahlig, Cheng Xie, Cindy Hong Li, Arvinder K Dhalla, Sridharan Rajamani, Nevena Mollova, Daniel Soohoo, Eve-Irene Lepist, Bernard Murray, Gerry Rhodes, Luiz Belardinelli, Manoj C Desai
Late sodium current (late INa) is enhanced during ischemia by reactive oxygen species (ROS) modifying the Nav 1.5 channel, resulting in incomplete inactivation. Compound 4 (GS-6615, eleclazine) a novel, potent, and selective inhibitor of late INa, is currently in clinical development for treatment of long QT-3 syndrome (LQT-3), hypertrophic cardiomyopathy (HCM), and ventricular tachycardia-ventricular fibrillation (VT-VF). We will describe structure-activity relationship (SAR) leading to the discovery of 4 that is vastly improved from the first generation late INa inhibitor 1 (ranolazine)...
October 3, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27667511/phenolic-acids-isolated-from-the-fungus-schizophyllum-commune-exert-analgesic-activity-by-inhibiting-voltage-gated-sodium-channels
#16
Hui-Min Yao, Gan Wang, Ya-Ping Liu, Ming-Qiang Rong, Chuan-Bin Shen, Xiu-Wen Yan, Xiao-Dong Luo, Ren Lai
The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp...
September 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27666389/fhf-independent-conduction-of-action-potentials-along-the-leak-resistant-cerebellar-granule-cell-axon
#17
Katarzyna Dover, Christopher Marra, Sergio Solinas, Marko Popovic, Sathyaa Subramaniyam, Dejan Zecevic, Egidio D'Angelo, Mitchell Goldfarb
Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials...
September 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27614087/preferential-conduction-block-of-myelinated-axons-by-nitric-oxide
#18
Peter Shrager, Margaret Youngman
Conduction block by nitric oxide (NO) was examined in myelinated and unmyelinated axons from both the central nervous system and peripheral nervous system. In rat vagus nerves, mouse optic nerves at P12-P23, adult and developing mouse sciatic nerves, and mouse spinal cords, myelinated fibers were preferentially blocked reversibly by concentrations of NO similar to those encountered in inflammatory lesions. The possibility that these differences between myelinated and unmyelinated axons are due to the normal developmental substitution of Na(+) channel subtype Nav 1...
September 10, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27598514/scn10a-mutation-in-a-patient-with-erythromelalgia-enhances-c-fiber-activity-dependent-slowing
#19
Andreas M Kist, Dagrun Sagafos, Anthony M Rush, Cristian Neacsu, Esther Eberhardt, Roland Schmidt, Lars Kristian Lunden, Kristin Ørstavik, Luisa Kaluza, Jannis Meents, Zhiping Zhang, Thomas Hedley Carr, Hugh Salter, David Malinowsky, Patrik Wollberg, Johannes Krupp, Inge Petter Kleggetveit, Martin Schmelz, Ellen Jørum, Angelika Lampert, Barbara Namer
Gain-of-function mutations in the tetrodotoxin (TTX) sensitive voltage-gated sodium channel (Nav) Nav1.7 have been identified as a key mechanism underlying chronic pain in inherited erythromelalgia. Mutations in TTX resistant channels, such as Nav1.8 or Nav1.9, were recently connected with inherited chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient's peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations...
2016: PloS One
https://www.readbyqxmd.com/read/27595042/scn2a-related-early-onset-epileptic-encephalopathy-responsive-to-phenobarbital
#20
Fiona M Baumer, Jurriaan M Peters, Christelle M El Achkar, Phillip L Pearl
Voltage-gated sodium channels (Nav) are critical regulators of neuronal excitability. Genes for the α-subunits of three sodium channel subtypes-SCN1A, SCN2A, and SCN3A-are all located on chromosome 2q24. A full-term boy with an unremarkable birth history presented at 1 month of age with unusual movements that had started on day of life 2. Exam was notable for lack of visual attention, hypotonia, and hyperreflexia. Electroencephalogram (EEG) showed an invariant burst suppression with multifocal spikes, ictal episodes with bicycling movements associated with buildups of rhythmic activity, and epileptic spasms...
March 2016: Journal of Pediatric Epilepsy
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