sodium channels

Summary

Summary: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes.

Top Publications

  1. pmc The crystal structure of a voltage-gated sodium channel
    Jian Payandeh
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    Nature 475:353-8. 2011
  2. ncbi Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels
    Zhi Gang Xiong
    Robert S Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
    Cell 118:687-98. 2004
  3. pmc Voltage-gated sodium channels at 60: structure, function and pathophysiology
    William A Catterall
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    J Physiol 590:2577-89. 2012
  4. ncbi International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
    Pharmacol Rev 57:397-409. 2005
  5. ncbi Spider-venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutic leads
    Julie K Klint
    Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Road, St Lucia, QLD 4072, Australia
    Toxicon 60:478-91. 2012
  6. ncbi Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues
    V Bennett
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Physiol Rev 81:1353-92. 2001
  7. ncbi The action potential in mammalian central neurons
    Bruce P Bean
    Harvard Medical School, Department of Neurobiology, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Rev Neurosci 8:451-65. 2007
  8. ncbi A model for human ventricular tissue
    K H W J ten Tusscher
    Department of Theoretical Biology, Utrecht University, 3584 CH Utrecht, The Netherlands
    Am J Physiol Heart Circ Physiol 286:H1573-89. 2004
  9. pmc Neurological perspectives on voltage-gated sodium channels
    Niels Eijkelkamp
    Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
    Brain 135:2585-612. 2012
  10. ncbi The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals
    ROBERT O'HAGAN
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Neurosci 8:43-50. 2005

Detail Information

Publications294 found, 100 shown here

  1. pmc The crystal structure of a voltage-gated sodium channel
    Jian Payandeh
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    Nature 475:353-8. 2011
    ..This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level...
  2. ncbi Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels
    Zhi Gang Xiong
    Robert S Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
    Cell 118:687-98. 2004
    ..Thus, acidosis injures the brain via membrane receptor-based mechanisms with resultant toxicity of [Ca2+]i, disclosing new potential therapeutic targets for stroke...
  3. pmc Voltage-gated sodium channels at 60: structure, function and pathophysiology
    William A Catterall
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    J Physiol 590:2577-89. 2012
    Voltage-gated sodium channels initiate action potentials in nerve, muscle and other excitable cells...
  4. ncbi International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
    Pharmacol Rev 57:397-409. 2005
    The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells...
  5. ncbi Spider-venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutic leads
    Julie K Klint
    Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Road, St Lucia, QLD 4072, Australia
    Toxicon 60:478-91. 2012
    ..01% of this diversity been characterised. Thus, it is likely that future research will reveal additional structural classes of spider-venom peptides that target Na(V) channels...
  6. ncbi Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues
    V Bennett
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Physiol Rev 81:1353-92. 2001
    ..Exciting questions for the future relate to the molecular basis for these pathways and their roles in a clinical context, either as the basis for disease or more positively as therapeutic targets...
  7. ncbi The action potential in mammalian central neurons
    Bruce P Bean
    Harvard Medical School, Department of Neurobiology, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Rev Neurosci 8:451-65. 2007
    ..Recent work offers an increasingly detailed understanding of how the expression of particular channel types underlies the remarkably diverse firing behaviour of various types of neurons...
  8. ncbi A model for human ventricular tissue
    K H W J ten Tusscher
    Department of Theoretical Biology, Utrecht University, 3584 CH Utrecht, The Netherlands
    Am J Physiol Heart Circ Physiol 286:H1573-89. 2004
    ..We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue...
  9. pmc Neurological perspectives on voltage-gated sodium channels
    Niels Eijkelkamp
    Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
    Brain 135:2585-612. 2012
    The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain...
  10. ncbi The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals
    ROBERT O'HAGAN
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Neurosci 8:43-50. 2005
    ..Our findings link the application of external force to the activation of a molecularly defined metazoan sensory transduction channel...
  11. ncbi An SCN9A channelopathy causes congenital inability to experience pain
    James J Cox
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Cambridge CB2 0XY, UK
    Nature 444:894-8. 2006
    ..Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit...
  12. ncbi The cell and molecular basis of mechanical, cold, and inflammatory pain
    Bjarke Abrahamsen
    Molecular Nociception Group, University College London UCL, Gower Street, London, WC1E 6BT, UK
    Science 321:702-5. 2008
    ..These data demonstrate that Na(v)1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing...
  13. pmc An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing
    Jamie D Kapplinger
    Department of Medicine, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota, USA
    Heart Rhythm 7:33-46. 2010
    ..Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype...
  14. pmc Localization and targeting of voltage-dependent ion channels in mammalian central neurons
    Helene Vacher
    Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, California 95616 8519, USA
    Physiol Rev 88:1407-47. 2008
    ..Finally, we discuss the emerging mechanisms for determining the discrete subcellular distributions observed for many neuronal ion channels...
  15. pmc ASIC3, a sensor of acidic and primary inflammatory pain
    Emmanuel Deval
    Institut de Pharmacologie Moleculaire et Cellulaire, UMR 6097 CNRS Université de Nice Sophia Antipolis, Sophia Antipolis, Valbonne, France
    EMBO J 27:3047-55. 2008
    ..Peripheral ASIC3 channels are thus essential sensors of acidic pain and integrators of molecular signals produced during inflammation where they contribute to primary hyperalgesia...
  16. ncbi Voltage-gated sodium channels and pain pathways
    John N Wood
    Molecular Nociception Group, Department of Biology, University College, Gower Street, London WC1E 6BT, UK
    J Neurobiol 61:55-71. 2004
    ..The peripheral input that drives pain perception thus depends on the presence of functional voltage-gated sodium channels. Remarkably, two voltage-gated sodium channel genes (Nav1.8 and Nav1...
  17. pmc Pickpocket is a DEG/ENaC protein required for mechanical nociception in Drosophila larvae
    Lixian Zhong
    Pharmacology Science Training Program, Duke University Medical Center, Durham, NC 27710, USA
    Curr Biol 20:429-34. 2010
    ..Our results suggest that neurons that detect harsh touch in Drosophila utilize similar mechanosensory molecules...
  18. ncbi Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation
    Wenqin Hu
    Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Nat Neurosci 12:996-1002. 2009
    ..Further modeling studies and simultaneous somatic and axonal recordings showed that distal Na(v)1.6 promotes action potential initiation, whereas proximal Na(v)1.2 promotes its backpropagation to the soma...
  19. ncbi The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways
    A N Akopian
    Molecular Nociception Group, Department of Biology, Medawar Building, University College, London WC1E 6BT, UK
    Nat Neurosci 2:541-8. 1999
    Many damage-sensing neurons express tetrodotoxin (TTX)-resistant voltage-gated sodium channels. Here we examined the role of the sensory-neuron-specific (SNS) TTX-resistant sodium channel alpha subunit in nociception and pain by ..
  20. ncbi Sodium channels in normal and pathological pain
    Sulayman D Dib-Hajj
    Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Annu Rev Neurosci 33:325-47. 2010
    ..Voltage-gated sodium channels, Na(v)1.1-Na(v)1.9, are essential for generation and conduction of electrical impulses in excitable cells...
  21. pmc Electrophysiology and beyond: multiple roles of Na+ channel β subunits in development and disease
    Gustavo A Patino
    Department of Pharmacology and Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, United States
    Neurosci Lett 486:53-9. 2010
    ..In short, these proteins, originally thought of as merely accessory to α subunits, are critical players in their own right in human health and disease. Here we discuss the role of VGSC β subunits in the nervous system...
  22. ncbi Relationship between kdr mutation and resistance to pyrethroid and DDT insecticides in natural populations of Anopheles gambiae
    Lisa Reimer
    Department of Entomology and Center for Vectorborne Diseases, University of California Davis, Davis, CA 95616, USA
    J Med Entomol 45:260-6. 2008
    ..Kdr-w conferred greater resistance to permethrin than kdr-e. We also describe a modified diagnostic designed to detect both resistant alleles simultaneously...
  23. pmc Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability
    Matthew S Grubb
    MRC Centre for Developmental Neurobiology, King s College London, 4th Floor, New Hunt s House, Guy s Campus, London SE1 1UL, UK
    Nature 465:1070-4. 2010
    ..with high extracellular potassium moves multiple components of the AIS, including voltage-gated sodium channels, up to 17 mum away from the soma of excitatory neurons...
  24. pmc Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes
    Priscila Y Sato
    Center for Arrhythmia Research, University of Michigan, 5025 Venture Dr, Ann Arbor, MI 48108, USA
    Circ Res 105:523-6. 2009
    ..Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na(V)1.5) to this region...
  25. ncbi Nomenclature of voltage-gated sodium channels
    A L Goldin
    Neuron 28:365-8. 2000
  26. ncbi Prevalence of long-QT syndrome gene variants in sudden infant death syndrome
    Marianne Arnestad
    Institute of Forensic Medicine, University of Oslo, Oslo, Norway
    Circulation 115:361-7. 2007
    ..Given the importance and potential implications of these observations, we performed a study to more accurately quantify the contribution to SIDS of LQTS gene mutations and rare variants...
  27. pmc Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel
    Arthur Beyder
    Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    J Physiol 588:4969-85. 2010
    ..These data suggest that mechanical activation of Na(v)1.5 results in dose-dependent voltage dependence shifts of activation and inactivation due to mechanical modulation of the voltage sensors...
  28. pmc Structural basis for gating charge movement in the voltage sensor of a sodium channel
    Vladimir Yarov-Yarovoy
    Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:E93-102. 2012
    ..We confirmed the validity of these structural models by comparing with a high-resolution structure of a NaChBac homolog and showing predicted molecular interactions of hydrophobic residues in the S4 segment in disulfide-locking studies...
  29. pmc Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel
    M E Gellens
    Department of Medicine, University of Pennsylvania, Philadelphia 19104
    Proc Natl Acad Sci U S A 89:554-8. 1992
    ..in Xenopus oocytes, hH1 exhibits rapid activation and inactivation kinetics similar to native cardiac sodium channels. The single channel conductance of hH1 to sodium ions is about twice that of the homologous rat channel and ..
  30. pmc NaV1.1 channels and epilepsy
    William A Catterall
    University of Washington, Department of Pharmacology, SJ 30, Seattle, WA 98195 7280, USA
    J Physiol 588:1849-59. 2010
    Voltage-gated sodium channels initiate action potentials in brain neurons, and sodium channel blockers are used in therapy of epilepsy...
  31. pmc Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat
    Shuangsong Hong
    Department of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 279:29341-50. 2004
    ..Alterations in the expression and function of voltage-gated tetrodotoxin-resistant (TTX-R) sodium channels have been implicated in animal models of neuropathic pain, including models of diabetic neuropathy...
  32. pmc Altered function of the SCN1A voltage-gated sodium channel leads to gamma-aminobutyric acid-ergic (GABAergic) interneuron abnormalities
    Melinda S Martin
    Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA
    J Biol Chem 285:9823-34. 2010
    Voltage-gated sodium channels are required for the initiation and propagation of action potentials...
  33. pmc Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model
    Anne Laure Leoni
    INSERM, UMR915, l institut du thorax, Nantes, France
    PLoS ONE 5:e9298. 2010
    ..We investigated the mechanisms of this heterogeneity in a mouse model with heterozygous targeted disruption of Scn5a (Scn5a(+/-) mice) and compared our results to those obtained in patients with loss-of-function mutations in SCN5A...
  34. pmc Cell-type-dependent molecular composition of the axon initial segment
    Andrea Lorincz
    Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary
    J Neurosci 28:14329-40. 2008
    ..This precise arrangement is likely to contribute to the diversity of firing properties observed among central neurons...
  35. pmc Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation
    Baron Chanda
    Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    J Gen Physiol 120:629-45. 2002
    ..These experiments allow us to map structural features onto the kinetic landscape of a sodium channel during activation...
  36. ncbi SCN5A channelopathies--an update on mutations and mechanisms
    Thomas Zimmer
    Institute of Physiology II, Friedrich Schiller University Jena, Kollegiengasse 9, 07743 Jena, Germany
    Prog Biophys Mol Biol 98:120-36. 2008
    ..Possible reasons for less convincing genotype-phenotype correlations are suggested...
  37. ncbi Neurosensory mechanotransduction
    Martin Chalfie
    Columbia University, Department of Biological Sciences, 1012 Fairchild Center, M C 2446, New York, New York 10027, USA
    Nat Rev Mol Cell Biol 10:44-52. 2009
    ..Current studies are directed towards characterizing these candidates, determining how they are mechanically gated and discovering new molecules that are involved in mechanical sensing...
  38. ncbi Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2
    J Spampanato
    Department of Microbiology and Molecular Genetics, University of California, Irvine, California 92697-4025, USA
    J Neurosci 21:7481-90. 2001
    ....
  39. ncbi Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction
    Yejia Song
    Division of Cardiovascular Medicine, University of Florida, 1600 SW Archer Rd, M 411, Gainesville, FL 32610 0277, USA
    J Pharmacol Exp Ther 318:214-22. 2006
    ....
  40. ncbi Acid-sensing ion channels in sensory perception
    Eric Lingueglia
    Institut de Pharmacologie Moleculaire et Cellulaire, CNRS Université de Nice Sophia Antipolis UMR 6097, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France
    J Biol Chem 282:17325-9. 2007
  41. ncbi Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice
    Marcus Mall
    Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, The University of North Carolina at Chapel Hill, 7011 Thurston Bowles Building, Chapel Hill, North Carolina 27599 7248, USA
    Nat Med 10:487-93. 2004
    ..We conclude that increasing airway Na(+) absorption initiates cystic fibrosis-like lung disease and produces a model for the study of the pathogenesis and therapy of this disease...
  42. ncbi Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system
    Manuel A Friese
    Medical Research Council Human Immunology Unit and Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK
    Nat Med 13:1483-9. 2007
    ..In addition, adoptive transfer of T cells from wild-type mice did not affect the protection mediated by Asic1 disruption. These results suggest that ASIC1 blockers could provide neuroprotection in multiple sclerosis...
  43. ncbi SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes
    Séverine Petitprez
    University of Bern, Department of Clinical Research, Murtenstrasse, 35, 3010 Bern, Switzerland
    Circ Res 108:294-304. 2011
    ..As dystrophin is absent at the intercalated discs, Na(v)1.5 could potentially interact with other, yet unknown, proteins at this site...
  44. pmc Sodium channel mutations in epilepsy and other neurological disorders
    Miriam H Meisler
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 0618, USA
    J Clin Invest 115:2010-7. 2005
    ..The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well...
  45. ncbi DDT, pyrethrins, pyrethroids and insect sodium channels
    T G E Davies
    Biological Chemistry Division, Rothamsted Research, Hertfordshire, UK
    IUBMB Life 59:151-62. 2007
    ..Here we review some of the work (done at Rothamsted Research and elsewhere) that has led to the identification of specific residues on the sodium channel that may constitute the DDT and pyrethroid binding sites...
  46. ncbi A mutation in the voltage-gated sodium channel gene associated with pyrethroid resistance in Latin American Aedes aegypti
    K Saavedra-Rodriguez
    Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA
    Insect Mol Biol 16:785-98. 2007
    ..The tools and information presented provide a means for early detection and characterization of kdr that is critical to the development of strategies for resistance management...
  47. ncbi Pyrethroid and DDT cross-resistance in Aedes aegypti is correlated with novel mutations in the voltage-gated sodium channel gene
    C Brengues
    Laboratoire de Lutte contre les Insectes Nuisibles, Institut de Recherche pour le Developpment, Montpellier, France
    Med Vet Entomol 17:87-94. 2003
    ..Direct neurophysiological assays on individual larvae from three strains with these mutations demonstrated reduced nerve sensitivity to permethrin or lambda cyhalothrin inhibition compared to the susceptible strains...
  48. ncbi Biology of cardiac sodium channel Nav1.5 expression
    Martin B Rook
    Department of Medical Physiology, Division Heart and Lungs, University Medical Center Utrecht, The Netherlands
    Cardiovasc Res 93:12-23. 2012
    ..The reviewed studies have provided valuable information on how the Na(v)1.5 expression level, localization, and biophysical properties are regulated, but also revealed that our understanding of the underlying mechanisms is still limited...
  49. pmc Overview of the voltage-gated sodium channel family
    Frank H Yu
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    Genome Biol 4:207. 2003
    Selective permeation of sodium ions through voltage-dependent sodium channels is fundamental to the generation of action potentials in excitable cells such as neurons...
  50. ncbi Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation
    Ikuo Ogiwara
    Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako, Saitama 351 0198, Japan
    J Neurosci 27:5903-14. 2007
    ..Our data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and, furthermore, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice...
  51. pmc Insect sodium channels and insecticide resistance
    Ke Dong
    Department of Entomology, Genetics Program and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
    Invert Neurosci 7:17-30. 2007
    Voltage-gated sodium channels are essential for the generation and propagation of action potentials (i.e., electrical impulses) in excitable cells...
  52. ncbi Acid-sensing ion channels (ASICs): pharmacology and implication in pain
    Emmanuel Deval
    Institut de Pharmacologie Moléculaire et Cellulaire IPMC, UMR 6097 CNRS Université de Nice Sophia Antipolis UNS, 660, route des Lucioles, 06560 Valbonne, France
    Pharmacol Ther 128:549-58. 2010
    ..Targeting ASIC channels at different levels of the nervous system could therefore be an interesting strategy for the relief of pain...
  53. ncbi Action potential generation requires a high sodium channel density in the axon initial segment
    Maarten H P Kole
    Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia
    Nat Neurosci 11:178-86. 2008
    ..In conclusion, action potential generation requires a high Na(+) channel density at the AIS, which is maintained by tight anchoring to the actin cytoskeleton...
  54. pmc Adaptive evolution of voltage-gated sodium channels: the first 800 million years
    Harold H Zakon
    Section of Neurobiology, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 109:10619-25. 2012
    ....
  55. pmc A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons
    Sylvie Diochot
    Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut Paul Hamel, Sophia Antipolis, Valbonne, France
    EMBO J 23:1516-25. 2004
    ..The ASIC3-like current in primary cultured sensory neurons is partly and reversibly inhibited by APETx2 with an IC50 of 216 nM, probably due to the mixed inhibitions of various co-expressed ASIC3-containing channels...
  56. ncbi Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations
    Y P Goldberg
    Xenon Pharmaceuticals Inc, 3650 Gilmore Way, Burnaby, BC V5G4W8, Canada
    Clin Genet 71:311-9. 2007
    ..From these prioritized candidate sodium channels, we identified 10 mutations in the SCN9A gene encoding the sodium channel protein Nav1.7...
  57. ncbi Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning
    John A Wemmie
    Department of Psychiatry, Neuroscience Graduate Program, Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA
    J Neurosci 23:5496-502. 2003
    ..These studies suggest that ASIC1 is distributed to regions supporting high levels of synaptic plasticity and contributes to the neural mechanisms of fear conditioning...
  58. ncbi Identification of a point mutation in the voltage-gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids
    H Ranson
    Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
    Insect Mol Biol 9:491-7. 2000
    ..The An. gambiae sodium channel was physically mapped to chromosome 2L, division 20C. This position corresponds to the location of a major quantitative trait locus determining resistance to permethrin in the Kenyan strain of An. gambiae...
  59. ncbi Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels
    P Escoubas
    Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, Sophia Antipolis, Valbonne, France
    J Biol Chem 275:25116-21. 2000
    ..The new toxin is the first high affinity and highly selective pharmacological agent for this novel class of ionic channels. It will be important for future studies of their physiological and physio-pathological roles...
  60. pmc Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons
    Christopher J Benson
    Department of Internal Medicine and Psychiatry, and Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 99:2338-43. 2002
    ..These data indicate that combinations of two or more DEG/ENaC subunits coassemble as heteromultimers to generate transient H(+)-gated currents in mouse DRG neurons...
  61. ncbi Architecture and pore block of eukaryotic voltage-gated sodium channels in view of NavAb bacterial sodium channel structure
    Denis B Tikhonov
    Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St Petersburg, Russia
    Mol Pharmacol 82:97-104. 2012
    ..Because the sequence similarity between eukaryotic and prokaryotic sodium channels in this region is poor, the structural similarity is unclear...
  62. ncbi Energy-efficient action potentials in hippocampal mossy fibers
    Henrik Alle
    Independent Hertie Research Group, Max Planck Institute for Brain Research, 60528 Frankfurt, Germany
    Science 325:1405-8. 2009
    ..Analysis of ionic conductance parameters revealed that the properties of Na+ and K+ channels are matched to make axonal action potentials energy-efficient, minimizing their contribution to activity-dependent metabolism...
  63. ncbi Presynaptic activity regulates Na(+) channel distribution at the axon initial segment
    Hiroshi Kuba
    Career Path Promotion Unit for Young Life Scientists, Kyoto University Graduate School of Medicine, Kyoto 606 8501, Japan
    Nature 465:1075-8. 2010
    ..Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation...
  64. ncbi Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels
    J A Wolf
    Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 21:1923-30. 2001
    ....
  65. ncbi Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels
    Stephan A Pless
    Department of Anesthesiology, University of British Columbia, 2350 Health Science Mall, Vancouver, British Columbia, V6T 1Z3 Canada
    Nat Commun 2:351. 2011
    Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs)...
  66. pmc Self-limited hyperexcitability: functional effect of a familial hemiplegic migraine mutation of the Nav1.1 (SCN1A) Na+ channel
    Sandrine Cestele
    Department of Neurophysiopathology, Besta Neurological Institute, 20133 Milan, Italy
    J Neurosci 28:7273-83. 2008
    ..Thus, we found a possible difference in the functional effects of FHM and familial epilepsy mutations of Nav1.1...
  67. pmc Detection of knockdown resistance (kdr) mutations in Anopheles gambiae: a comparison of two new high-throughput assays with existing methods
    Chris Bass
    Department of Biological Chemistry, Rothamsted Research, Harpenden, UK
    Malar J 6:111. 2007
    ..However, there are few reports comparing the performance of these different assays. In this study, two new high-throughput assays were developed and compared with four established techniques...
  68. pmc Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)
    D Woodrow Benson
    Department of Pediatrics, Cincinnati Children s Hospital, Ohio, USA
    J Clin Invest 112:1019-28. 2003
    ..Biophysical characterization of the mutants using heterologously expressed recombinant human heart sodium channels demonstrate loss of function or significant impairments in channel gating (inactivation) that predict reduced ..
  69. ncbi TNF-α contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury
    Xin Hua He
    Pain Research Center and Department of Physiology, Zhongshan School of Medicine of Sun Yat Sen University, Guangzhou, PR China
    Pain 151:266-79. 2010
    ..discharges of action potentials in primary afferents, resulted from the abnormal expression of voltage gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons following peripheral nerve injury are important for the ..
  70. ncbi Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures
    Katharina Zimmermann
    Department of Physiology and Pathophysiology, Faculty of Medicine, Friedrich Alexander University Erlangen Nuremberg, 91054 Erlangen, Germany
    Nature 447:855-8. 2007
    ..Our data present strong evidence for a specialized role of Na(v)1.8 in nociceptors as the critical molecule for the perception of cold pain and pain in the cold...
  71. pmc Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia
    Y Yang
    Department of Dermatology, Peking University First Hospital, Beijing, China
    J Med Genet 41:171-4. 2004
    ..SCN9A, encoding a voltage-gated sodium channel alpha subunit predominantly expressed in sensory and sympathetic neurones, may play an important role in nociception and vasomotor regulation...
  72. ncbi The roles of sodium channels in nociception: implications for mechanisms of neuropathic pain
    Min Liu
    Wolfson Institute for Biomedical Research, University College, London, UK
    Pain Med 12:S93-9. 2011
    ..7, Nav1.8, and Nav1.9) could potentially reduce the side effect profile. Individual isoforms of voltage-gated sodium channels have been linked to particular types of pain. Nav1...
  73. ncbi Enhanced locomotion caused by loss of the Drosophila DEG/ENaC protein Pickpocket1
    Joshua A Ainsley
    Department of Physiology and Biophysics, University of Iowa, Roy J and Lucille A Carver College of Medicine, Iowa City, IA 52242, USA
    Curr Biol 13:1557-63. 2003
    ....
  74. pmc Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects
    Miriam H Meisler
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 5618, USA
    J Physiol 588:1841-8. 2010
    ..Whole genome sequencing and exome sequencing in patients with epilepsy will soon make it possible to detect multiple variants and their interactions in the genomes of patients with seizure disorders...
  75. ncbi Genetic variation in SCN10A influences cardiac conduction
    John C Chambers
    Department of Epidemiology and Public Health, Imperial College London, UK
    Nat Genet 42:149-52. 2010
    ..05) and a lower risk of ventricular fibrillation (P = 0.01). Our findings provide new insight into the pathogenesis of cardiac conduction, heart block and ventricular fibrillation...
  76. ncbi Transport and localization of the DEG/ENaC ion channel BNaC1alpha to peripheral mechanosensory terminals of dorsal root ganglia neurons
    J Garcia-Anoveros
    Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    J Neurosci 21:2678-86. 2001
    ..brain sodium channel (BNaC, also known as BNC/ASIC) proteins form acid-sensitive and amiloride-blockable sodium channels that are related to putative mechanosensory channels...
  77. pmc Nav channel mechanosensitivity: activation and inactivation accelerate reversibly with stretch
    Catherine E Morris
    Neuroscience, Ottawa Health Research Institute, Ottawa, Ontario, Canada
    Biophys J 93:822-33. 2007
    Voltage-gated sodium channels (Nav) are modulated by many bilayer mechanical amphiphiles, but whether, like other voltage-gated channels (Kv, HCN, Cav), they respond to physical bilayer deformations is unknown...
  78. pmc Molecular identity of dendritic voltage-gated sodium channels
    Andrea Lorincz
    Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary
    Science 328:906-9. 2010
    ..Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability...
  79. pmc Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans
    Hiroshi Watanabe
    Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Clin Invest 118:2260-8. 2008
    ..Sodium current was lower when NaV1.5 was coexpressed with mutant beta1 or beta1B subunits than when it was coexpressed with WT subunits. These findings implicate SCN1B as a disease gene for human arrhythmia susceptibility...
  80. pmc Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons
    Anthony M Rush
    NeuroSolutions Ltd, PO Box 3517, Coventry CV4 7ZS, UK
    J Physiol 579:1-14. 2007
    ..The pattern of expression of sodium channels differs in different subclasses of DRG neurons and is not fixed but, on the contrary, changes in response to ..
  81. ncbi ERK1/2 mitogen-activated protein kinase phosphorylates sodium channel Na(v)1.7 and alters its gating properties
    Severine Stamboulian
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Neurosci 30:1637-47. 2010
    Na(v)1.7 sodium channels can amplify weak stimuli in neurons and act as threshold channels for firing action potentials...
  82. pmc Seizure termination by acidosis depends on ASIC1a
    Adam E Ziemann
    Medical Scientist Training Program, University of Iowa, Iowa City, Iowa 52242, USA
    Nat Neurosci 11:816-22. 2008
    ..Our results identify ASIC1a as an important element in seizure termination when brain pH falls and suggest both a molecular mechanism for how the brain stops seizures and new therapeutic strategies...
  83. ncbi Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders
    Massimo Mantegazza
    Dipartimento di Neurofisiopatologia, Fondazione Istituto Neurologico C Besta, Milano, Italy
    Lancet Neurol 9:413-24. 2010
    Voltage-gated sodium channels (VGSCs) are key mediators of intrinsic neuronal and muscle excitability...
  84. ncbi Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy
    Frank H Yu
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
    Nat Neurosci 9:1142-9. 2006
    Voltage-gated sodium channels (Na(V)) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in Na(V)1.1 channels cause severe myoclonic epilepsy in infancy (SMEI)...
  85. ncbi Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis
    Scott P Fraser
    Neuroscience Solutions to Cancer Research Group, Department of Biological Sciences, Imperial College London, UK
    Clin Cancer Res 11:5381-9. 2005
    ..The purpose of this study was to investigate voltage-gated Na(+) channel (VGSC) expression and its possible role in human breast cancer...
  86. pmc A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome
    Nanda A Singh
    Department of Human Genetics, University of Utah, Salt Lake City, Utah, United States of America
    PLoS Genet 5:e1000649. 2009
    ..This study provides evidence for a role of SCN9A in human epilepsies, both as a cause of FS and as a partner with SCN1A mutations...
  87. pmc GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9
    Johan A R Ostman
    Centre for Neuroscience, Institute of Cell and Molecular Science, Queen Mary University of London, Newark Street, London E1 2AT, UK
    J Physiol 586:1077-87. 2008
    ..9 underlies the G-protein pathway-regulated TTX-r persistent Na(+) current in small diameter sensory neurones that may drive spontaneous discharge in nociceptive nerve fibres during inflammation...
  88. pmc Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases
    Zhi Gang Xiong
    Robert S Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
    Curr Opin Pharmacol 8:25-32. 2008
    ..This review provides an overview of the recent advance in electrophysiological, pharmacological characterization of ASICs, and their role in neurological diseases. Therapeutic potential of current available ASIC inhibitors is discussed...
  89. ncbi The local differentiation of myelinated axons at nodes of Ranvier
    Sebastian Poliak
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    Nat Rev Neurosci 4:968-80. 2003
    ..This local differentiation of myelinated axons is tightly regulated by oligodendrocytes and myelinating Schwann cells, and is achieved through complex mechanisms that are used by another specialized cell-cell contact - the synapse...
  90. ncbi Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons
    Michelino Puopolo
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 27:645-56. 2007
    ..The results also show a significant contribution of subthreshold TTX-sensitive sodium current...
  91. ncbi Impaired impulse propagation in Scn5a-knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging
    Toon A B van Veen
    Heart Lung Center, Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands
    Circulation 112:1927-35. 2005
    ..The SCN5A sodium channel is a major determinant for cardiac impulse propagation. We used epicardial mapping of the atria, ventricles, and septae to investigate conduction velocity (CV) in Scn5a heterozygous young and old mice...
  92. ncbi Annexin II light chain regulates sensory neuron-specific sodium channel expression
    Kenji Okuse
    Department of Biology, University College London, Gower Street, London WC1E 6BT, UK
    Nature 417:653-6. 2002
    ..Unlike other sodium channels, Na(V)1.8 is poorly expressed in cell lines even in the presence of accessory beta-subunits...
  93. ncbi Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations
    Carol Ann Remme
    Department of Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Trends Cardiovasc Med 18:78-87. 2008
    ..Here, we provide an overview of current knowledge on SCN5A mutations associated with sodium channel overlap syndromes and discuss a possible role for modifiers in determining disease expressivity in the individual patient...
  94. ncbi The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN) in nociceptive primary afferent neurons
    Xin Fang
    Department of Physiology, University of Bristol, Medical School, Bristol BS8 1TD, United Kingdom
    J Neurosci 22:7425-33. 2002
    ..The data provide direct evidence that Na(v)1.9 is expressed selectively in (but not in all) C- and A-fiber nociceptive-type units and suggest that Na(v)1.9 contributes to membrane properties that are typical of nociceptive neurons...
  95. ncbi The mammalian sodium channel BNC1 is required for normal touch sensation
    M P Price
    Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA
    Nature 407:1007-11. 2000
    ..These data identify the BNC1 channel as essential for the normal detection of light touch and indicate that BNC1 may be a central component of a mechanosensory complex...
  96. pmc A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat
    Michael F Jarvis
    Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064, USA
    Proc Natl Acad Sci U S A 104:8520-5. 2007
    Activation of tetrodotoxin-resistant sodium channels contributes to action potential electrogenesis in neurons. Antisense oligonucleotide studies directed against Na(v)1...
  97. pmc Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is reexpressed following axotomy
    S G Waxman
    Department of Neurology, Yale University School of Medicine, New Haven 06510
    J Neurophysiol 72:466-70. 1994
    ..1. In situ hybridization with subtype-specific probes was used to ask whether there is a change in the types of sodium channels that are expressed in dorsal root ganglion (DRG) neurons after axotomy. 2...
  98. ncbi Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study
    Ruben Coronel
    Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, The Netherlands
    Circulation 112:2769-77. 2005
    ..The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown...
  99. ncbi Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice
    E Hummler
    Institut de Pharmacologie et de Toxicologie de l Université, Lausanne, Switzerland
    Nat Genet 12:325-8. 1996
    ..In vitro, assembly and expression of functional active sodium channels in the Xenopus oocyte is strictly dependent on alpha-ENaC--the beta and gamma subunits by themselves are ..
  100. pmc Structure-function map of the receptor site for β-scorpion toxins in domain II of voltage-gated sodium channels
    Joel Z Zhang
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
    J Biol Chem 286:33641-51. 2011
    ..Molecular determinants of β-scorpion toxin (CssIV) binding and action on rat brain sodium channels are located in the S1-S2 (IIS1-S2) and S3-S4 (IIS3-S4) extracellular linkers of the voltage-sensing module in ..
  101. ncbi Sodium channels and microglial function
    Joel A Black
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06511, USA
    Exp Neurol 234:302-15. 2012
    ..These studies also provide strong evidence that Nav1.6 is the predominant sodium channel isoform expressed in microglia and that its activity contributes to the response of microglia to multiple activating signals...

Research Grants74

  1. Transcription factors regulating sensory gene expression and pain pathways
    Eric E Turner; Fiscal Year: 2011
    ..Other examples include specialized sodium channels of the Nav family, with roles in inflammatory pain and in the transmission of pain at low temperatures, and ..
  2. Exercise training and blood pressure in hypertension: integrated mechanisms
    Noreen F Rossi; Fiscal Year: 2012
    ....
  3. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..Understanding the mechanisms of action of this family will provide significant insights into the control of ion balance and other essential processes, and may reveal novel strategies to develop anti-hypertensive therapies. ..
  4. Epithelial Sodium Channels in the Supraoptic Vasopressin and Oxytocin Neurons
    Ryoichi Teruyama; Fiscal Year: 2009
    ..PUBLIC HEALTH RELEVANCE Epithelial sodium channels which present in kidney and which play an important role in development of hypertension in human, have been ..
  5. Characterization of the ER associated Biogenesis and Degradation of ENaC
    Teresa M Buck; Fiscal Year: 2013
    ..Mutations in ENaC lead to diseases including Liddle's Syndrome and Pseudohypoaldosteronism Type 1;therefore, understanding the early biogenesis events is critical. ..
  6. GILZ Regulation of ENaC
    David Pearce; Fiscal Year: 2012
    ..This work will shed new light on the basic mechanisms, and provide avenues for better treatment of high blood pressure and edema. ..
  7. Combined neuroprotection and metabolic correction to treat leukodystrophies
    ERNESTO ROQUE BONGARZONE; Fiscal Year: 2013
    ....
  8. Regulation of ENaC Transcription
    Bruce C Kone; Fiscal Year: 2013
    ..This proposal examines a novel network of interacting proteins in the cell nucleus that regulate transcription, the initial molecular step in generating this protein. ..
  9. A Functional Role for the Circadian Clock Protein Per1 in the Regulation of ??ENa
    Michelle L Gumz; Fiscal Year: 2013
    ..By characterizing the role of the circadian clock protein Per1 in the regulation of renal sodium transport, we can begin to understand the connection between the circadian clock, kidney function and blood pressure. ..
  10. Regulation of ENaC in salt-sensitive hypertension via inflammation-induced ROS pr
    TENGIS SANALOVICH PAVLOV; Fiscal Year: 2013
    ..The K99/R00 grant fits to my career goals providing excellent opportunity to assist in transitioning to a stable independent research position with NIH or other independent research funding. ..
  11. VOLTAGE SENSITIVE SODIUM CHANNELS IN BRAIN
    William A Catterall; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Sodium channels initiate electrical signals required for information processing in the nervous system, contraction of ..
  12. Epigenic Control of ENaC Transcription and Sodium Transport
    Wenzheng Zhang; Fiscal Year: 2013
    ....
  13. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2013
    ..This grant funds studies of epilepsies caused by genetic mutations in sodium channels, a type of protein important for generating electrical impulses in the brain.
  14. Epithelial Sodium Channels in Vasopressin and Oxytocin Synthesizing Magnocellular
    Ryoichi Teruyama; Fiscal Year: 2013
    ..Results from this proposed project will provide critical information concerning central ENaC inhibition as a potential new target in the treatment of cardiovascular disease (10). ..
  15. Cell Surface Plasminogen Activation and Hypertension
    Robert J Parmer; Fiscal Year: 2013
    ....
  16. TRAFFIC REGULATORY PROTEINS AND ENAC
    Raymond A Frizzell; Fiscal Year: 2013
    ..This work is expected to reveal new regulators and therapeutic targets for the control of sodium and fluid transport in the kidney. ..
  17. Role of Insulin Receptors in the Kidney
    CAROLYN MARY ECELBARGER; Fiscal Year: 2013
    ..Moreover, they may provide insight into the pathology underlying hypertension associated with the metabolic syndrome. ..
  18. SGK Regulation of Epithelial Sodium Transport
    David Pearce; Fiscal Year: 2013
    ..C) Examine the role of mTOR in regulation of amiloride-inhibitable currents in isolated CCD using patch clamp. ..
  19. Angiotensin converting enzyme, angiotensin II, and arrhythmia
    Samuel C Dudley; Fiscal Year: 2010
    ..This phenotype is associated with reductions in cardiac sodium channels. We have developed preliminary data that Angll-mediated oxidative stress activates the transcription factor ..
  20. Neuron-specific block of T-type calcium channels
    Edward Perez-Reyes; Fiscal Year: 2012
    ..The research team includes Dr. Edward Perez- Reyes, a T-channel expert, Dr. Guanping Gao, an AAV expert, and Dr. Hui-Lin Pan, a neuropathic pain expert. ..
  21. Molecular and Cellular Determinants of the Exercise Pressor Reflex in CHF
    Irving H Zucker; Fiscal Year: 2013
    ..Furthermore, w believe that these data will uncover new targets for therapy in CHF. ..
  22. Human Macrophage Sodium Channels: Novel Targets for Inflammatory Diseases
    Michael D Carrithers; Fiscal Year: 2013
    ..Recently, we identified two novel variants of voltage-gated sodium channels, NaV1.5 and NaV1.6, that are expressed in human macrophages and may represent novel pharmacologic targets...
  23. Blood Pressure Regulation by the Circadian Clock Protein Per1
    Michelle L Gumz; Fiscal Year: 2013
    ..These studies have the potential to identify a novel target for the treatment of hypertension and will yield insight into the mechanism of how the circadian clock contributes to the regulation of blood pressure. ..
  24. ENaC Transport in Insulin Resistance: Role of Insulin &IGF-1 Receptors
    Vivek Bhalla; Fiscal Year: 2013
    ....
  25. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William A Catterall; Fiscal Year: 2013
    ..We will examine new-generation, subtype-selective GABA-A receptor activators and test effectiveness of these therapies approaches to control seizures and co-morbidities in DS mice. ..
  26. Physiological mechanisms responsible for cognitive impairments in Dravet Syndrome
    Pierre Pascal Lenck-Santini; Fiscal Year: 2013
    Voltage gated Sodium channels (Nav) are critical for the initiation and propagation of action potentials. Mutations of the SCN1A gene, which codes for Nav type 1...
  27. SODIUM ENTRY INTO AMILORIDE-SENSITIVE EPITHELIA
    Catherine M Fuller; Fiscal Year: 2013
    ..Epithelial sodium channels (ENaC) have been found in other sodium transportinmg epithelia, e.g...
  28. Molecular Dissection of Calmodulin Domain Functions
    Madeline A Shea; Fiscal Year: 2013
    ..We propose three Aims focused on sodium channels found in the central nervous system (CNS)...
  29. CHLORIDE CHANNELS IN LUNG DEVELOPMENT
    Pamela L Zeitlin; Fiscal Year: 2012
    ..The product of this work will be a method of stimulating chloride transport to compensate for mutant CFTR, reduce sodium absorption and relieve airway inflammation in vivo. ..
  30. STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
    Adrian Gross; Fiscal Year: 2013
    ..founders of a large superfamily of structurally related ion channels that includes nucleotide gated channels, sodium channels, and calcium channels...
  31. SERT KO rats are a model of sex specific visceral pain
    James J Galligan; Fiscal Year: 2013
    ..interactions between 5-HT and estrogen on sensory neurons that lead to upregulation of tetrodotoxin-resistant sodium channels. These studies will show that increased 5-HT availability in female SERT KO rats alters visceral sensitivity ..
  32. Transcriptomics and Population Genetics of Mosquito Resistance to Pyrethroids
    Mariangela Bonizzoni; Fiscal Year: 2013
    ..gambiae mosquitoes from Kenya. This project will significantly enhance the knowledge of the molecular mechanism of insecticide resistance in An. gambiae, and may lead to the development of more reliable resistance monitoring tools. ..
  33. Toxic metals and ion channels in cigarette-smoke induced COPD
    ESTELLE A CORMET BOYAKA; Fiscal Year: 2010
    ..We found that cadmium can suppress the Cystic Fibrosis Transmembrane conductance Regulator, a chloride channel that when dysfunctional leads to cystic fibrosis. (End of Abstract) ..
  34. The Role of Stress in a Genetically Predisposed Epilepsy Model
    NIKKI TAMARA SAWYER; Fiscal Year: 2013
    ..This proposal aims to investigate the relationship between a genetic predisposition to epilepsy and the stress response, with the goal of identifying new therapeutic targets for the treatment of epilepsy. ..
  35. Voltage-Gating in Bacterial Ion Channels
    Ana M Correa; Fiscal Year: 2010
    ....
  36. Modulation of the Epithelial Sodium Channel by Proteases and Peptide Inhibitors
    CHRISTOPHER JOHN PASSERO; Fiscal Year: 2010
    ..In the kidney, two distinct pools of epithelial sodium channels are inserted into the apical membrane of the principal cells of the collecting duct...
  37. Congenital Myasthenic Syndromes: Pathogenic Mechanisms
    RICARDO ANIBAL MASELLI; Fiscal Year: 2013
    ....
  38. Development of High Affinity Analogues of Brevenal: Novel Molecular Probes for Ne
    Mary C Wolf; Fiscal Year: 2011
    ..PbTxs) and ciguatoxins (CTXs) are well known as the only ligands known to bind to site 5 on voltage-gated sodium channels (VGSCs) with high affinity...
  39. Phase II Therapeutic Trial of Mexiletine
    Richard J Barohn; Fiscal Year: 2010
    ..Mexiletine is a class 1B antiarrhythmic medication that has high affinity for muscle sodium channels. In vitro data indicates that mexiletine corrects delayed inactivation of sodium channels in common NDM ..
  40. Epithelial Sodium Channel Trafficking
    Peter M Snyder; Fiscal Year: 2013
    ..This may have important implications for our understanding and treatment of diseases including hypertension and cystic fibrosis. ..
  41. Role of Sodium Channel SCN1B in Inherited Epilepsy
    Lori L Isom; Fiscal Year: 2013
    ..These results will have positive impact because these identified roles will lead to greater understanding of the mechanisms of GEFS+-spectrum diseases and may lead to novel therapeutic agents for epilepsy. ..
  42. Human mesenchymal stem cell microvesicles for the treatment of acute lung injury
    Jae Woo Lee; Fiscal Year: 2013
    ..Furthermore, the results may provide preclinical data that could facilitate development of MSC MV as a therapy for ALI. ..
  43. The mechanistic basis of non-invasive deep brain stimulation by ultrasound
    MERRITT C MADUKE; Fiscal Year: 2012
    ..focused ultrasound (a non-invasive technology capable of deep brain penetration) can activate voltage-gated sodium channels (Nav channels) and consequently increase the rate of action potential firing in the mouse motor cortex in ..
  44. Sodium Channels and Cardiac Arrhythmias
    Isabelle Deschenes; Fiscal Year: 2013
    ..2. Investigate the mechanisms by which SCN5A polymorphisms can modulate the function of mutated sodium channels. 3. Develop gene therapy approaches, using genetic polymorphisms, to rescue dysfunctional channels...
  45. Therapeutic effects of ketogenic diet in a mouse model of severe myoclinic epilep
    Franck K Kalume; Fiscal Year: 2013
    ..diet;3) to investigate the effects of ketogenic diet on the function of 'brain' voltage-gated sodium channels. RELEVANCE (Seeinstructions): These studies will advance the understanding of the mechanisms of action of ..
  46. Blood Pressure Regulation by OAT3
    Volker Vallon; Fiscal Year: 2013
    ..We will also identify selective OAT3- blocking substances and explore their ability to reduce blood pressure - such substances could potentially be useful in the treatment of patients with hypertension. ..
  47. Protective activity of the lectin-like domain of TNF in permeability edema
    Rudolf Lucas; Fiscal Year: 2013
    ....
  48. Role of serum- and glucocorticoid-regulated kinase-1 in electrical remodeling
    Anthony Rosenzweig; Fiscal Year: 2013
    ..Thus understanding SGK1's role in the heart could have important practical implications, and the current application would help advance our understanding of the potential of SGK1 as a therapeutic target. ..
  49. REGULATION OF SIGNALING BY CELL SURFACE PROTEOLYSIS
    Nigel W Bunnett; Fiscal Year: 2011
    ..The proposal will provide new information that will facilitate the treatment, detection and diagnosis of inflammatory diseases that are a global cause of morbidity and mortality. ..
  50. Stem cell derived neurons and inherited epilepsy
    Miriam H Meisler; Fiscal Year: 2010
    ..After the molecular features of the abnormality are characterized, it may become possible to use these cultured neurons to screen for drugs which can prevent the progression of this disabling disease. ..
  51. Physiologic role of the gamma epithelial sodium channel subunit in the kidney
    Donald E Kohan; Fiscal Year: 2010
    ..This work has the potential to uncover mechanisms involved in the development and/or maintenance of hypertension and disorders of potassium excretion. ..
  52. Genetic Regulation of Complex Neurological Diseases
    Wayne N Frankel; Fiscal Year: 2013
    ..In parallel, we will explore whether CELF4 has a coordinating role in shaping cellular responses by examining mutant cell culture, acute brain slice and whole animal models of neuronal plasticity. ..
  53. Phosphorylation-dependent regulation of epithelial sodium channel (ENaC) traffick
    Xiubin Liang; Fiscal Year: 2012
    ..Through this study, we will advance our understanding of molecular mechanisms of ENaC regulation and the results will provide further insight into the control of sodium balance, blood volume and thereby of blood pressure. ..
  54. Characterization of the sodium channel mutations involved in insecticide resistan
    Nannan Liu; Fiscal Year: 2011
    ..A large number of studies showed that point mutations of sodium channels reduce sodium channel sensitivity to pyrethroid insecticides and that, in turn, such mutations confer ..
  55. Local anesthetic receptor in peripheral Na+ channels
    GING K WANG; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: The local anesthetic receptor in peripheral sodium channels is an important target for clinical drugs used in local anesthesia and in pain management...
  56. REGULATION OF SIGNALING BY CELL-SURFACE PROTEOLYSIS
    Nigel W Bunnett; Fiscal Year: 2010
    ..The proposal will provide new information which is beneficial for the detection, diagnosis and treatment of inflammatory diseases that are a global cause of morbidity and mortality. ..
  57. Design, Synthesis and Evaluation of Novel Isoform-Selective Sodium Channel Inhibi
    JOHN VINCENT MULCAHY; Fiscal Year: 2013
    ..7 as a target for pain treatment, and 3) a high-affinity, isoform-selective sodium channel antagonist as a lead compound for optimization toward a next-generation pain therapeutic. ..
  58. A Total Synthesis of Gambierol Using an Epoxide-Opening Cascade Approach
    DENISE ANN COLBY; Fiscal Year: 2010
    ..An increased understanding of ion channel structure and function could lead to treatments for arrhythmia and disorders of the central nervous system. ..
  59. Rational polytherapy in the treatment of cholinergic seizures
    Claude G Wasterlain; Fiscal Year: 2013
    ..R025-6981 or felbamate), and 3/ an anticonvulsant acting at a non-GABA site such as rapidly inactivating sodium channels (valproate);or slowly inactivating sodium channels (lacosamide);or potassium channels (ezogabine);or ..
  60. Molecular Physiology of Myotonia and Periodic Paralysis
    Stephen C Cannon; Fiscal Year: 2013
    ....
  61. Late Sodium Current Blockade in High-Risk ICD Patients - DCC
    Arthur J Moss; Fiscal Year: 2013
    ..Conducting such a trial might open the door to the development of an entire line of compounds targeting the late sodium current as their main mode of anti-arrhythmic action. ..
  62. Regulation of Epithelial Sodium Channel by CFTR chloride channel
    Bakhrom Berdiev; Fiscal Year: 2009
    ....
  63. PHARMACOTHERAPY FOR XEROSTOMIA IN SJOGREN'S SYNDROME
    SAMUEL HOPKINS; Fiscal Year: 2005
    ..Ultimately, our goal is the full clinical development of 552-02 as a first-line therapy for patients suffering from xerostomia associated with Sjogren's syndrome. ..
  64. DEVELOPMENT OF NOVEL ANTIEPILEPTIC DRUGS
    Manoj K Patel; Fiscal Year: 2010
    ..Since sodium channels control cellular excitability, they have become important targets for the suppression of seizures...
  65. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    ALFRED GEORGE; Fiscal Year: 2009
    Voltage-gated sodium channels are heteromultimeric integral membrane proteins that are responsible for the initial phase of the action potential in most excitable cells...
  66. IN VIVO ACTIONS OF ANTIARRHYTHMIC DRUGS
    Dan Roden; Fiscal Year: 1990
    Although the interaction between antiarrhythmic drugs and cardiac sodium channels has been intensively studied in vitro, the effects of these agents on sodium channel-dependent phenomena in the cardiac syncytium is less well-..
  67. Sodium Channel Contratoxins Derived from Cone Snail Venoms
    Grzegorz Bulaj; Fiscal Year: 2007
    ..potent paralytic agents that act by binding to the same site on, and blocking the function of voltage-gated sodium channels. We propose to develop a conceptually novel antagonist of these and related neurotoxins...
  68. MODULATION OF SODIUM CHANNELS BY G PROTEINS
    Todd Scheuer; Fiscal Year: 2001
    ..b>Sodium channels are responsible for the initial depolarization of the action potential in most neurons...
  69. Trigeminal Neuropathic Pain Mechanisms
    Michael Henry; Fiscal Year: 2006
    ..A recent focus of pain research is examining changes in the expression of sodium channels that follow nerve injury since these changes may contribute to neuronal hyperexcitability and the development ..
  70. CONOPEPTIDE SODIUM CHANNEL BLOCKERS FOR CHRONIC PAIN
    James Garrett; Fiscal Year: 2000
    DESCRIPTION (adapted from applicant's abstract): We propose to develop conopeptide blockers of voltage gated sodium channels for the treatment of chronic pain. Conopeptides are bioactive peptides isolated from marine cone snail venom...
  71. ACTIONS OF INSECTICIDES ON SODIUM CHANNEL ISOFORMS
    DAVID SODERLUND; Fiscal Year: 2000
    ..cause toxic effects in vertebrate nerves and muscles by modifying the normal function of voltage-sensitive sodium channels. Sodium channels exist in multiple isoforms that exhibit differential tissue distribution and developmental ..
  72. Mice with Human SCN1A Alleles Generated by Recombinase-Mediated Cassette Exchange
    Jennifer A Kearney; Fiscal Year: 2010
    Mutations in voltage-gated sodium channels have been implicated in several types of human epilepsy with varying degrees of clinical severity...
  73. DEVELOPMENT OF EPITHELIAL SODIUM CHANNEL BLOCKERS FOR CF
    Judith St George; Fiscal Year: 2006
    ..Our preliminary data support the hypothesis that 552-02 is a potent, selective inhibitor of epithelial sodium channels that is effective in enhancing mucociliary clearance and is well tolerated when administered as a single dose ..