SCN3A

Summary

Gene Symbol: SCN3A
Description: sodium channel, voltage-gated, type III, alpha subunit
Alias: NAC3, Nav1.3, brain III voltage-gated sodium channel, sodium channel protein brain III subunit alpha, sodium channel protein type 3 subunit alpha, sodium channel protein type III subunit alpha, sodium channel, voltage-gated, type III, alpha polypeptide, voltage-gated sodium channel subtype III, voltage-gated sodium channel subunit alpha Nav1.3
Species: human

Top Publications

  1. ncbi Voltage-gated sodium channels in taste bud cells
    Na Gao
    Senomyx, Inc, 4767 Nexus Centre Drive, San Diego, CA 92121, USA
    BMC Neurosci 10:20. 2009
  2. ncbi Differential evolution of voltage-gated sodium channels in tetrapods and teleost fishes
    Jenny Widmark
    Department of Neuroscience, Uppsala University, Uppsala, Sweden
    Mol Biol Evol 28:859-71. 2011
  3. ncbi Human and rat Nav1.3 voltage-gated sodium channels differ in inactivation properties and sensitivity to the pyrethroid insecticide tefluthrin
    Jianguo Tan
    Insecticide Toxicology Laboratory, Department of Entomology, New York State Agricultural Experiment Station, 630 W North St, Cornell University, Geneva, NY 14456, USA
    Neurotoxicology 30:81-9. 2009
  4. ncbi [Expression and function of voltage-gated Na+ channel isoforms in rat sinoatrial node]
    Xin Huang
    Department of Cardiology, First Affiliated Hospital, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Medical School of Xi an Jiaotong University, Xi an 710061, China
    Nan Fang Yi Ke Da Xue Xue Bao 27:52-5. 2007
  5. ncbi Transport characteristics of N-acetyl-L-aspartate in rat astrocytes: involvement of sodium-coupled high-affinity carboxylate transporter NaC3/NaDC3-mediated transport system
    Takuya Fujita
    Department of Biochemical Pharmacology, Kyoto Pharmaceutical University, Jamashina ku, Kyoto, Japan
    J Neurochem 93:706-14. 2005
  6. ncbi Vasa recta voltage-gated Na+ channel Nav1.3 is regulated by calmodulin
    Whaseon Lee-Kwon
    Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA
    Am J Physiol Renal Physiol 292:F404-14. 2007
  7. ncbi Differential expression of exon 5 splice variants of sodium channel alpha subunit mRNAs in the developing mouse brain
    E V Gazina
    Howard Florey Institute, The University of Melbourne, 3010, Victoria, Australia
    Neuroscience 166:195-200. 2010
  8. ncbi TNF-? 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
  9. ncbi Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav1.3 in DRG neurons in vivo and in vitro
    Ying Zang
    Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat Sen University, 74 Zhongshan Rd 2, Guangzhou 510080, PR China
    Brain Res 1363:151-8. 2010
  10. ncbi The sodium channel {beta}3-subunit induces multiphasic gating in NaV1.3 and affects fast inactivation via distinct intracellular regions
    Fiona S Cusdin
    Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom
    J Biol Chem 285:33404-12. 2010

Research Grants

  1. Trigeminal Neuropathic Pain Mechanisms
    Michael Henry; Fiscal Year: 2006
  2. Scn8a and Seizure Resistance
    Alan L Goldin; Fiscal Year: 2010
  3. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2010
  4. Molecular Properties of Voltage-Sensitive Calcium Channels
    William A Catterall; Fiscal Year: 2010
  5. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William Catterall; Fiscal Year: 2001
  6. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William A Catterall; Fiscal Year: 2010
  7. Regulation of Cardiac Calcium Channels by an Autoinhibitory Signaling Complex
    William A Catterall; Fiscal Year: 2010
  8. Receptor Sites and Antagonists for Paralytic Neurotoxins
    William Catterall; Fiscal Year: 2007
  9. VOLTAGE SENSITIVE SODIUM CHANNELS IN BRAIN
    William Catterall; Fiscal Year: 2007
  10. Gene interaction in development and disease
    MIRIAM MEISLER; Fiscal Year: 2007

Scientific Experts

Detail Information

Publications79

  1. ncbi Voltage-gated sodium channels in taste bud cells
    Na Gao
    Senomyx, Inc, 4767 Nexus Centre Drive, San Diego, CA 92121, USA
    BMC Neurosci 10:20. 2009
    ..The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown...
  2. ncbi Differential evolution of voltage-gated sodium channels in tetrapods and teleost fishes
    Jenny Widmark
    Department of Neuroscience, Uppsala University, Uppsala, Sweden
    Mol Biol Evol 28:859-71. 2011
    ..of amniotes, generating the cluster SCN5A, SCN10A, and SCN11A on one chromosome and the cluster SCN1A, SCN2A, SCN3A, and SCN9A on a different chromosome...
  3. ncbi Human and rat Nav1.3 voltage-gated sodium channels differ in inactivation properties and sensitivity to the pyrethroid insecticide tefluthrin
    Jianguo Tan
    Insecticide Toxicology Laboratory, Department of Entomology, New York State Agricultural Experiment Station, 630 W North St, Cornell University, Geneva, NY 14456, USA
    Neurotoxicology 30:81-9. 2009
    ....
  4. ncbi [Expression and function of voltage-gated Na+ channel isoforms in rat sinoatrial node]
    Xin Huang
    Department of Cardiology, First Affiliated Hospital, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Medical School of Xi an Jiaotong University, Xi an 710061, China
    Nan Fang Yi Ke Da Xue Xue Bao 27:52-5. 2007
    ..To detect the expression of voltage-gated Na(+) channel (NaCh) isoforms in rat sinoatrial node and explore their functions...
  5. ncbi Transport characteristics of N-acetyl-L-aspartate in rat astrocytes: involvement of sodium-coupled high-affinity carboxylate transporter NaC3/NaDC3-mediated transport system
    Takuya Fujita
    Department of Biochemical Pharmacology, Kyoto Pharmaceutical University, Jamashina ku, Kyoto, Japan
    J Neurochem 93:706-14. 2005
    ..of astrocytes from rat cerebral cortex and the involvement of NA+-coupled high-affinity carboxylate transporter NaC3 (formerly known as NaDC3) responsible for N-acetyl-L-aspartate transport...
  6. ncbi Vasa recta voltage-gated Na+ channel Nav1.3 is regulated by calmodulin
    Whaseon Lee-Kwon
    Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA
    Am J Physiol Renal Physiol 292:F404-14. 2007
    ..3C was not affected by Ca(2+) concentration. We conclude that Na(V)1.3 is expressed by DVR, binds to CaM, and is regulated by CaM and Ca(2+). Inhibition of CaM binding suppresses pericyte Na(V) currents...
  7. ncbi Differential expression of exon 5 splice variants of sodium channel alpha subunit mRNAs in the developing mouse brain
    E V Gazina
    Howard Florey Institute, The University of Melbourne, 3010, Victoria, Australia
    Neuroscience 166:195-200. 2010
    Sodium channel alpha subunit genes expressed in the human brain, SCN1A, SCN2A, SCN3A and SCN8A, are subject to alternative splicing of coding exons 5N and 5A...
  8. ncbi TNF-? 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
    ..These data suggest that increased TNF-? may be responsible for up-regulation of Nav1.3 and Nav1.8 in uninjured DRG neurons following nerve injury...
  9. ncbi Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav1.3 in DRG neurons in vivo and in vitro
    Ying Zang
    Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat Sen University, 74 Zhongshan Rd 2, Guangzhou 510080, PR China
    Brain Res 1363:151-8. 2010
    ..The data suggested that injury to ventral root might lead to neuropathic pain and the re-expression of Nav1.3 in primary sensory neurons by activation of NF-?B...
  10. ncbi The sodium channel {beta}3-subunit induces multiphasic gating in NaV1.3 and affects fast inactivation via distinct intracellular regions
    Fiona S Cusdin
    Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom
    J Biol Chem 285:33404-12. 2010
    ..The complex gating behavior induced by ?3 may contribute to the known hyperexcitability of peripheral neurons under those physiological conditions where expression of ?3 and Na(v)1.3 are both enhanced...
  11. ncbi Patterned electrical activity modulates sodium channel expression in sensory neurons
    Joshua P Klein
    Department of Neurology and PVA EPVA Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Neurosci Res 74:192-8. 2003
    ..These results show that a change in neuronal activity can alter the expression of sodium channel genes in a subtype-specific manner, via a mechanism independent of NGF withdrawal...
  12. ncbi Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer
    Rui Gao
    Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P R China
    Oncol Rep 23:1293-9. 2010
    ..Our findings suggested that abnormal expression of Nav1.5 could be an integral component of the metastatic process in human ovarian cancer and might serve as a therapeutic target in ovarian cancer treatment...
  13. ncbi Familial neonatal seizures with intellectual disability caused by a microduplication of chromosome 2q24.3
    Sarah E Heron
    SA Pathology at Women s and Children s Hospital, Adelaide, South Australia, Australia
    Epilepsia 51:1865-9. 2010
    ..Characterization revealed a 1.57 Mb duplication at 2q24.3 containing eight genes including SCN2A, SCN3A, and the 3¢ end of SCN1A...
  14. ncbi Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons
    Tetsuo Fukuoka
    Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663 8501, Japan
    J Comp Neurol 510:188-206. 2008
    ..3 induction was independent of either TrkA or GFRalpha1 expression, suggesting that the induction of Nav1.3 may be one of the common responses of axotomized DRG neurons without a direct relationship to NGF/GDNF supply...
  15. ncbi Molecular and functional characterization of voltage-gated sodium channels in human sperm
    Francisco M Pinto
    Instituto de Investigaciones Quimicas, CSIC, Sevilla, Spain
    Reprod Biol Endocrinol 7:71. 2009
    ..We have investigated the expression of voltage-gated sodium channels in human spermatozoa and characterized their role in sperm motility...
  16. ncbi Increased late sodium currents are related to transcription of neuronal isoforms in a pressure-overload model
    Yutao Xi
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi an Jiaotong University, 277 West Yanta Road, Xi an, Shaanxi, China
    Eur J Heart Fail 11:749-57. 2009
    ..However, the underlying mechanism of late I(Na) (I(NaL)) production remains uncertain. We hypothesized that transcriptional alteration among sodium channel (NaCh) isoforms may contribute to I(NaL) in failing cardiomyocytes...
  17. ncbi Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression
    Patrick Kwan
    Division of Neurology, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
    Pharmacogenet Genomics 18:989-98. 2008
    ..We investigated the association of AED responsiveness with genetic polymorphisms and correlated any association with mRNA expression of the neuronal sodium channels...
  18. ncbi Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy
    Devang Kashyap Thakor
    Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095 1668, USA
    Mol Pain 5:14. 2009
    ..We have hypothesized that altered local expression of NaV1.8 in the peripheral axons of DRG neurons could facilitate nociceptive signal generation and propagation after neuropathic injury...
  19. ncbi Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy
    Katherine D Holland
    Division of Neurology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Neurosci Lett 433:65-70. 2008
    Mutations in the sodium channel genes SCN1A and SCN2A have been identified in monogenic childhood epilepsies, but SCN3A has not previously been investigated as a candidate gene for epilepsy...
  20. ncbi Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice
    Mohammed A Nassar
    Molecular Nociception Group, Department of Biology, University College London WC1E 6BT, UK
    Mol Pain 2:33. 2006
    ..Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of Nav1.3 in global knock-out mice. Our data demonstrate that Nav1.3 is neither necessary nor sufficient for the development of nerve-injury related pain...
  21. ncbi Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas
    Joel A Black
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, USA
    Ann Neurol 64:644-53. 2008
    ..We also examined the expression of two mitogen-activated protein (MAP) kinases, activated p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2), which are known to contribute to chronic pain, within these human neuromas...
  22. ncbi Neuropathic pain: emerging treatments
    A Dray
    AstraZeneca Research and Development, 7171 Frederick Banting Street, Montreal, Canada
    Br J Anaesth 101:48-58. 2008
    ..Finally of note is the emergence of biological approaches, for example, antibodies, siRNA, gene therapy, offering powerful therapeutic additions with which to redress the neurological disease imbalances causing neuropathic pain...
  23. ncbi Sodium channel activity modulates multiple functions in microglia
    Joel A Black
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, Connecticut 06518, USA
    Glia 57:1072-81. 2009
    ..6) indicate that Nav1.6 plays a role in microglial migration. The results demonstrate that the activity of sodium channels contributes to effector roles of activated microglia...
  24. ncbi Ralfinamide administered orally before hindpaw neurectomy or postoperatively provided long-lasting suppression of spontaneous neuropathic pain-related behavior in the rat
    Shi Hong Zhang
    Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, PR China
    Pain 139:293-305. 2008
    ..3, Nav1.7, Nav1.8, and Cav2.2 channels in rat DRG neurons, inhibition of substance P release from spinal cord synaptosomes, NMDA receptor antagonism and neuroprotection...
  25. ncbi Proteomic profiling of neuromas reveals alterations in protein composition and local protein synthesis in hyper-excitable nerves
    Hong Lei Huang
    Molecular Nociception Group, NPP Department, UCL, Gower Street, London WC1E6BT, UK
    Mol Pain 4:33. 2008
    ..An altered repertoire of protein expression, local protein synthesis and topological re-arrangements of ion channels may all play important roles in neuroma hyper-excitability...
  26. ncbi Altered expression of sodium channel distribution in the dorsal root ganglion after gradual elongation of rat sciatic nerves
    Katsunori Ohno
    Department of Orthopedic Surgery, Osaka Medical College, 2 7, Daigaku machi, Takatsuki 569 8686, Japan
    J Orthop Res 28:481-6. 2010
    ..Our findings indicate that Nav1.8 downregulation may be one of the pathophysiological mechanisms involved in limb lengthening-induced neuropathy...
  27. ncbi Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5
    Joel A Black
    Neuroscience Research Centre Bldg 34, VA Connecticut Healthcare System 127A, 950 Campbell Avenue, West Haven, CT 06516, USA
    Brain 133:835-46. 2010
    ..Our observations suggest that the upregulated expression of Nav1.5 in astrocytes may provide a compensatory mechanism, which supports sodium/potassium pump-dependent ionic homoeostasis in areas of central nervous system injury...
  28. ncbi Molecular differential expression of voltage-gated sodium channel ? and ? subunit mRNAs in five different mammalian cell lines
    Debora Baroni
    Istituto di Biofisica, CNR, Via De Marini, 6, 16149, Genoa, Italy
    J Bioenerg Biomembr 43:729-38. 2011
    ..This data provide a standard for the study of the modulation of the sodium channel expression in mammalian excitable tissues...
  29. ncbi Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation
    Tetsuo Fukuoka
    Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
    Pain 153:68-79. 2012
    ..Because neuropathic pain behaviors were developed by rats with SNL but not the sham-operation, the small number of injured L4 neurons likely do not contribute to the pathomechanisms of neuropathic pain...
  30. ncbi Infantile epilepsy associated with mosaic 2q24 duplication including SCN2A and SCN3A
    Marilena Vecchi
    Pediatric Neurology and Clinical Neurophysiology Unit, Department of Pediatrics, University of Padova, Italy
    Seizure 20:813-6. 2011
    ..3q24.3 involving SCN2A and SCN3A genes. Additional analyses (radiolabeled RFLP and quantitative PCR) confirmed the mosaicism of the duplication...
  31. ncbi Propranolol blocks cardiac and neuronal voltage-gated sodium channels
    Dao W Wang
    Department of Medicine, Vanderbilt University School of Medicine Nashville, TN, USA
    Front Pharmacol 1:144. 2010
    ..5 channels. Our findings establish sodium channels as targets for propranolol and may help explain some beneficial effects of the drug in treating cardiac arrhythmias, and may explain certain adverse central nervous system effects...
  32. ncbi Refractory neonatal epilepsy with a de novo duplication of chromosome 2q24.2q24.3
    Akihisa Okumura
    Department of Pediatrics, Juntendo University Faculty of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo, Japan
    Epilepsia 52:e66-9. 2011
    ..3-Mb duplication of 2q24.2q24.3, where at least 22 genes including a cluster of voltage-gated sodium channel genes (SCN1A, SCN2A, SCN3A, SCN7A, and SCN9A) and one noncoding RNA are located.
  33. ncbi Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3 expression and decreasing spinal microglial activation
    Kuang I Cheng
    Division of Plastic and Reconstructive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
    BMC Neurol 11:71. 2011
    ..Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain...
  34. ncbi [Role of voltage-sodium channels in neuropathic pain]
    Wen ting Shou
    Key Laboratory of Medical Neurobiology of Ministry of Health of China, China
    Zhejiang Da Xue Xue Bao Yi Xue Ban 40:217-21. 2011
    ..Here we reviewed the roles of sodium channels in neuropathic pain, which may be applicable for the development of new drugs with enhanced efficacy for neuropathic pain treatment...
  35. ncbi Neuropathic Nav1.3-mediated sensitization to P2X activation is regulated by protein kinase C
    Gary Mo
    Montreal Neurological Institute and The Alan Edwards Centre for Research on Pain, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
    Mol Pain 7:14. 2011
    ..Here we demonstrate the contribution of PKC to P2X-evoked VGSC activation in dorsal root ganglion (DRG) neurons in neuropathic conditions...
  36. ncbi Promoter analysis of mouse Scn3a gene and regulation of the promoter activity by GC box and CpG methylation
    Guang Fei Deng
    Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and The Ministry of Education of China, Institute of Neuroscience and The Second Affiliated Hospital of GuangZhou Medical University, 250 Chang gang dong Road, Guangzhou, China
    J Mol Neurosci 44:115-21. 2011
    ..The expression of mouse Scn3a product (Na(v)1.3) mainly occurs in embryonic and early postnatal brain but not in adult brain...
  37. ncbi Disruption of the SCN2A and SCN3A genes in a patient with mental retardation, neurobehavioral and psychiatric abnormalities, and a history of infantile seizures
    M Bartnik
    Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
    Clin Genet 80:191-5. 2011
    ..aCGH), we have identified a de novo ~110-kb deletion involving exons 1-2 of SCN2A and non-coding exon 1a of SCN3A in a 25-year-old female with mental retardation, neurobehavioral and psychiatric abnormalities, and a history of ..
  38. ncbi Laminae-specific distribution of alpha-subunits of voltage-gated sodium channels in the adult rat spinal cord
    T Fukuoka
    Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1 1 Mukogawa cho, Nishinomiya, Hyogo 663 8501, Japan
    Neuroscience 169:994-1006. 2010
    ..Comparison with our previous data concerning the subpopulation-specific distribution of Nav transcripts in primary afferent neurons provides potentially specific targets for local analgesics at the peripheral nerve and spinal levels...
  39. ncbi A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons
    Mark Estacion
    Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA
    Exp Neurol 224:362-8. 2010
    ..b>SCN3A, the gene which encodes Na(V)1.3, is part of this cluster, but until recently was not associated with any mutation...
  40. ncbi 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
    ..A small number of mutations have been found in SCN2A, SCN3A and SCN9A, and studies in the mouse suggest that SCN8A may also contribute to seizure disorders...
  41. ncbi Array-CGH detection of a de novo 2.8 Mb deletion in 2q24.2-->q24.3 in a girl with autistic features and developmental delay
    Chih Ping Chen
    Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan
    Eur J Med Genet 53:217-20. 2010
    ..8 Mb de novo deletion of chromosome 2q24.2-->q24.3 detected by array-CGH. This region contains two neuronal voltage-gated sodium channel genes SCN2A and SCN3A.
  42. ncbi Upregulation of Nav1.3 Channel Induced by rrTNF in Cultured Adult Rat DRG Neurons via p38 MAPK and JNK Pathways
    Ying Zang
    Pain Research Center and Department of Physiology, Zhongshan Medical School, Sun Yat Sen University, Guangzhou 510080, Guangdong, People s Republic of China
    Chin J Physiol 54:241-6. 2011
    ..3 completely (P<0.001). These data show that the activation of both p38 MAPK and JNK in DRG neurons was involved in the re-expression of Nav1.3 channel triggered by TNF-?, which might contribute to neuropathic pain...
  43. ncbi Voltage-gated sodium channel Nav1.1, Nav1.3 and beta1 subunit were up-regulated in the hippocampus of spontaneously epileptic rat
    Feng Guo
    Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Shenyang 110001, China
    Brain Res Bull 75:179-87. 2008
    ..The results of this study may be of value in revealing components of the molecular mechanisms of hippocampal excitation that are related to genetic epilepsy...
  44. ncbi SCN1A mutations and epilepsy
    John C Mulley
    Department of Genetic Medicine, Women s and Children s Hospital, North Adelaide, South Australia, Australia
    Hum Mutat 25:535-42. 2005
    SCN1A is part of the SCN1A-SCN2A-SCN3A gene cluster on chromosome 2q24 that encodes for alpha pore forming subunits of sodium channels. The 26 exons of SCN1A are spread over 100 kb of genomic DNA...
  45. ncbi Three brain sodium channel alpha-subunit genes are clustered on the proximal segment of mouse chromosome 2
    D Malo
    Department of Biochemistry, McGill University, Montreal, Canada
    Genomics 10:666-72. 1991
    ..Physical mapping by pulsed-field gel electrophoresis has established that Scn2a and Scn3a (genes encoding type II and type III sodium channel alpha-subunit isoforms) are physically linked and are ..
  46. ncbi Molecular diversity of voltage-gated sodium channel alpha subunits expressed in neuronal and non-neuronal excitable cells
    I Mechaly
    I N S E R M U583, Institut des Neurosciences de Montpellier Hôpital St Eloi, 80, rue Augustin Fliche, 34295 Montpellier Cedex 5, France
    Neuroscience 130:389-96. 2005
    ....
  47. 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
    ..Taken together, these data suggest that isotype-specific sodium channel blockers could be useful analgesics...
  48. ncbi Contactin associates with sodium channel Nav1.3 in native tissues and increases channel density at the cell surface
    Bhaval S Shah
    Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Neurosci 24:7387-99. 2004
    ..We propose that the upregulation of contactin and its colocalization with Na(v)1.3 in axotomized DRG neurons may contribute to the hyper-excitablity of the injured neurons...
  49. ncbi Requirement of neuronal- and cardiac-type sodium channels for murine sinoatrial node pacemaking
    Ming Lei
    University Laboratory of Physiology, University of Oxford, OX1 3PT, UK
    J Physiol 559:835-48. 2004
    ..1) and cardiac Nav1.5 isoforms are involved in pacemaking, although the cardiac Nav1.5 isoform alone is involved in the propagation of the action potential from the SA node to the surrounding atrial muscle...
  50. ncbi Expression of the sodium channel beta3 subunit in injured human sensory neurons
    Maria A Casula
    Peripheral Neuropathy Unit, Imperial College London, Area A, Ground Floor, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK
    Neuroreport 15:1629-32. 2004
    ..beta3-subunit expression may thus be regulated differently from beta1, beta2 and Nav1.8. Targeting beta3 interactions with key alpha-subunits, particularly Nav1.3 and Nav1.8, may provide novel selective analgesics...
  51. ncbi Upregulation of sodium channel Nav1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury
    Bryan C Hains
    Department of Neurology and Paralyzed Veterans of America Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Neurosci 23:8881-92. 2003
    ..3 expression and neuronal hyperexcitability associated with central neuropathic pain...
  52. ncbi Sodium channels SCN1A, SCN2A and SCN3A in familial autism
    L A Weiss
    Department of Human Genetics, University of Michigan, 4708 Medical Science II, Ann Arbor, MI 48109 0618, USA
    Mol Psychiatry 8:186-94. 2003
    ..SNP density was 1/kb in the genomic sequence screened. We report 38 sodium channel SNPs that will be useful in future association and linkage studies...
  53. ncbi Functional modulation of human brain Nav1.3 sodium channels, expressed in mammalian cells, by auxiliary beta 1, beta 2 and beta 3 subunits
    L S Meadows
    Montreal Neurological Institute, McGill University, Montreal, QC, Canada
    Neuroscience 114:745-53. 2002
    ..The results of this study support the hypothesis that Na(v)1.3 may mediate this fast sodium current...
  54. ncbi Changes in the mRNAs encoding voltage-gated sodium channel types II and III in human epileptic hippocampus
    W R Whitaker
    Department of Neurobiology, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
    Neuroscience 106:275-85. 2001
    ..However, it is likely that such changes would affect the intrinsic excitability of hippocampal neurones...
  55. ncbi Genomic structures of SCN2A and SCN3A - candidate genes for deafness at the DFNA16 locus
    N Kasai
    Department of Otolaryngology, Okayama University Medical School, 700 8558, Okayama, Japan
    Gene 264:113-22. 2001
    ..members of the voltage-gated sodium channel family, the type 2 alpha subunit (SCN2A) and the type 3 alpha subunit (SCN3A)...
  56. ncbi Cloning, distribution and functional analysis of the type III sodium channel from human brain
    Y H Chen
    Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK
    Eur J Neurosci 12:4281-9. 2000
    ..The distinct properties of the channel, together with its wide distribution in adult brain, suggest that in humans, type III may have important physiological roles under normal, and perhaps also pathological conditions...
  57. ncbi A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33
    S Baulac
    INSERM U289, Hopital de la Salpetriere, Paris Cedex, France
    Am J Hum Genet 65:1078-85. 1999
    ..Four genes coding for different isoforms of the alpha-subunit voltage-gated sodium channels (SCN1A, SCN2A1, SCN2A2, and SCN3A) located in this region are strong candidates for the disease gene.
  58. ncbi Isolation of a human-brain sodium-channel gene encoding two isoforms of the subtype III alpha-subunit
    C M Lu
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, USA
    J Mol Neurosci 10:67-70. 1998
    ..that this transcript represents the two isoforms (neonatal and adult) of the human brain sodium channel gene, SCN3A (GenBank accession numbers AF035685 and AF035686)...
  59. ncbi A new sodium channel alpha-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2
    M C Beckers
    Department of Biochemistry, McGill University, Montreal, H3G 1Y6, Canada
    Genomics 36:202-5. 1996
    ....
  60. ncbi Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31
    M S Malo
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Proc Natl Acad Sci U S A 91:2975-9. 1994
    ..assign this sequence as a part of a gene coding the alpha-subunit of a human brain type III sodium channel (SCN3A)...
  61. ncbi Contactin regulates the current density and axonal expression of tetrodotoxin-resistant but not tetrodotoxin-sensitive sodium channels in DRG neurons
    Anthony M Rush
    Department of Neurology, Yale School of Medicine, LCI 707, 333 Cedar St, New Haven, CT 06510, USA
    Eur J Neurosci 22:39-49. 2005
    ....
  62. ncbi Sodium channels and nociception: recent concepts and therapeutic opportunities
    Douglas S Krafte
    Icagen Inc, P O Box 14487, Research Triangle Park, NC 27709, USA
    Curr Opin Pharmacol 8:50-6. 2008
    ..All of these data are converging to suggest next generation sodium channel blockers may offer the potential for novel pain therapies in the future...
  63. ncbi The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy
    Melinda S Martin
    Department of Human Genetics, Emory University, Atlanta, GA 30322, USA
    Hum Mol Genet 16:2892-9. 2007
    ..four voltage-gated sodium channel genes that are primarily expressed in the central nervous system: SCN1A, SCN2A, SCN3A and SCN8A...
  64. ncbi Expression of Nav1.1 in rat retinal AII amacrine cells
    Yuko Kaneko
    Department of Physiology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Iruma gun, Saitama 350 0495, Japan
    Neurosci Lett 424:83-8. 2007
    ..Therefore, we combined ISH with immunohistochemistry and discovered that most of the PV-immunoreactive cells located at the INL/IPL border express Nav1.1. Our results show that AII amacrine cells express Nav1.1...
  65. ncbi Functional and molecular characterization of voltage-gated sodium channels in uteri from nonpregnant rats
    Marian Seda
    Instituto de Investigaciones Quimicas, 41092 Sevilla, Spain
    Biol Reprod 77:855-63. 2007
    ..Using end-point and real-time quantitative RT-PCR, we detected the presence of the VGSC alpha subunits Scn2a1, Scn3a, Scn5a, and Scn8a in the cDNA from longitudinal muscle...
  66. ncbi Sodium channel expression and the molecular pathophysiology of pain after SCI
    Bryan C Hains
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, and Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA
    Prog Brain Res 161:195-203. 2007
    ..3 dysregulation contributes to post-SCI chronic pain. If proven to be similar in humans, targeting of this system after SCI may offer hope for treatment of clinical pain...
  67. ncbi Differentiated pattern of sodium channel expression in dissociated Purkinje neurons maintained in long-term culture
    Mark Fry
    Department of Physiology, Queen s University, Kingston, Ontario, Canada
    J Neurochem 101:737-48. 2007
    ..4, Nav 1.5 or Nav1.8 Na+ channel alpha subunit gene expression in cultured Purkinje neurons, as observed in vivo. Together, the results indicate that key aspects of Na+ channel expression in mature Purkinje neurons in vivo occur in vitro...
  68. ncbi Downregulation of neuronal sodium channel subunits Nav1.1 and Nav1.6 in the sinoatrial node from volume-overloaded heart failure rat
    Yuan Du
    Department of Cardiovascular Medicine, First Hospital of Xi an Jiaotong University, No 277 West Yanta Road, Xi an, Shaanxi, 710061, China
    Pflugers Arch 454:451-9. 2007
    ..1 and Nav1.6 expression contributes to HF-induced SAN dysfunction. These findings provide additional information about molecular basis of disease-related impairment of SAN function...
  69. ncbi Isolation and structure-activity of mu-conotoxin TIIIA, a potent inhibitor of tetrodotoxin-sensitive voltage-gated sodium channels
    Richard J Lewis
    Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
    Mol Pharmacol 71:676-85. 2007
    ..TIIIA and analogs provide new biochemical probes as well as insights into the structure-activity of mu-conotoxins...
  70. ncbi Sodium channel expression in the ventral posterolateral nucleus of the thalamus after peripheral nerve injury
    Peng Zhao
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA
    Mol Pain 2:27. 2006
    ..3 sodium channel increases the excitability of VPL neurons injury, contributing to neuropathic pain...
  71. ncbi Immunolocalization of NaV1.2 channel subtypes in rat and cat brain and spinal cord with high affinity antibodies
    Miranda Jarnot
    Department of Neuroscience, Cell Biology and Physiology, Wright State University, 3640 Col Glenn Highway, Dayton, OH 45435, USA
    Brain Res 1107:1-12. 2006
    ..Specific staining was limited to fibers located in the granule and molecular layer, in an orientation consistent with granule cell unmyelinated axon labeling...
  72. ncbi Identification of functional voltage-gated Na(+) channels in cultured human pulmonary artery smooth muscle cells
    Oleksandr Platoshyn
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, 9500 Gilman Drive, MC 0725, San Diego, La Jolla, CA 92093 0725, USA
    Pflugers Arch 451:380-7. 2005
    ..Whether their expression and/or activity are heightened in the pathological state is discussed...
  73. ncbi Functional and molecular identification of sodium-coupled dicarboxylate transporters in rat primary cultured cerebrocortical astrocytes and neurons
    Etsuo Yodoya
    Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina ku, Kyoto, Japan
    J Neurochem 97:162-73. 2006
    ..Of these transporters, NaC3 (formerly known as Na+-coupled dicarboxylate transporter 3, NaDC3/SDCT2) and NaC2 (formerly known as Na+-coupled ..
  74. ncbi Fire and phantoms after spinal cord injury: Na+ channels and central pain
    Stephen G Waxman
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA
    Trends Neurosci 29:207-15. 2006
    ....
  75. ncbi Changes in electrophysiological properties and sodium channel Nav1.3 expression in thalamic neurons after spinal cord injury
    Bryan C Hains
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA
    Brain 128:2359-71. 2005
    ....
  76. 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
    ..This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties...
  77. ncbi Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction
    M Gotthardt
    Department of Molecular Genetics and Pathology, University of Texas Southwestern Medical Center, Dallas 75390-9046, USA
    J Biol Chem 275:25616-24. 2000
    ..They form the basis for the elucidation of the molecular pathways by which cells respond to the diversity of ligands that bind to these multifunctional receptors on the cell surface...
  78. ncbi Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences
    Melinda S Martin
    Department of Human Genetics, Emory University, Atlanta, GA 30322, USA
    Genomics 90:225-35. 2007
    The human voltage-gated sodium channel gene cluster on chromosome 2q24 contains three paralogs, SCN1A, SCN2A, and SCN3A, which are expressed in the central nervous system...
  79. ncbi Distribution and functional characterization of human Nav1.3 splice variants
    R Thimmapaya
    Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064, USA
    Eur J Neurosci 22:1-9. 2005
    ..This study has demonstrated that all four human splice variants of the Nav1.3 channel alpha subunit are widely expressed and generate functional TTX-sensitive Na+ channels that likely modulate cellular excitability...

Research Grants87

  1. Trigeminal Neuropathic Pain Mechanisms
    Michael Henry; Fiscal Year: 2006
    ..Identification of specific sodium channel alterations after injury may help develop more selective treatments for neuropathic pain. ..
  2. Scn8a and Seizure Resistance
    Alan L Goldin; Fiscal Year: 2010
    ..in the sodium channel SCN1A are a major cause of GEFS+ and SMEI, even though three other sodium channels (SCN2A, SCN3A, and SCN8A) are expressed in the central nervous system (CNS)...
  3. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2010
    ..The experimental sequence begins with studies to elucidate the functional consequences of novel SCN3A mutations associated with genetic epilepsy syndromes (Specific Aim 1)...
  4. Molecular Properties of Voltage-Sensitive Calcium Channels
    William A Catterall; Fiscal Year: 2010
    ....
  5. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William Catterall; Fiscal Year: 2001
    ..These results will be essential for understanding the molecular basis of expression and localization of sodium channels. ..
  6. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William A Catterall; Fiscal Year: 2010
    ..This project will use a mouse genetic model of this disease to determine how this gene defect causes epilepsy and to test new drug combinations for control of this intractable epilepsy syndrome. ..
  7. Regulation of Cardiac Calcium Channels by an Autoinhibitory Signaling Complex
    William A Catterall; Fiscal Year: 2010
    ..This information will provide the essential basic science background for translational research aimed at preventing and treating cardiovascular disease. ..
  8. Receptor Sites and Antagonists for Paralytic Neurotoxins
    William Catterall; Fiscal Year: 2007
    ....
  9. VOLTAGE SENSITIVE SODIUM CHANNELS IN BRAIN
    William Catterall; Fiscal Year: 2007
    ..These proposed studies will give new insight into the molecular mechanisms of sodium channel gating and its modification by second messenger-activated protein phosphorylation. ..
  10. Gene interaction in development and disease
    MIRIAM MEISLER; Fiscal Year: 2007
    ..Because of the high level of alternative splicing in the nervous system, variation in SCNM1 may be of particular significance for neurological disease. ..
  11. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William Catterall; Fiscal Year: 2006
    ..Our results will add substantially to understanding of the cell biology of the Na channel and the functional significance of Na channel signaling complexes. ..
  12. Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
    MIRIAM MEISLER; Fiscal Year: 2009
    ..This project will characterize the neurological and behavioral effects of specific changes in sodium channel genes, using mouse models of human mutations. ..
  13. VOLTAGE-SENSITIVE SODIUM CHANNELS IN BRAIN
    William Catterall; Fiscal Year: 1991
    ..These studies will provide essential information to understanding the molecular basis of electrical excitability...
  14. GENETIC REGULATION OF MOUSE ENZYMES
    MIRIAM MEISLER; Fiscal Year: 1991
    ..These investigations will contribute to our understanding of the molecular basis of tissue-specific and hormonal regulation of mammalian gene expression...
  15. MOLECULAR PROPERTIES OF VOLTAGE-SENSITIVE CA++ CHANNELS
    William Catterall; Fiscal Year: 1990
    ..These results will provide a basis for analysis of the molecular basis of calcium channel function and physiological regulation...
  16. VOLTAGE-SENSITIVE SODIUM CHANNELS IN BRAIN
    William Catterall; Fiscal Year: 1980
    ..These experiments will greatly enhance knoledge of the basic molecular mechanisms responsible for electrical excitability...
  17. TRAINING IN MOLECULAR NEUROBIOLOGY
    William Catterall; Fiscal Year: 2007
    ..The training program will integrate the substantial expertise of this group of faculty in a coordinated pre-doctoral and post-doctoral training effort. ..
  18. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William Catterall; Fiscal Year: 1992
    ..The results will define the functional roles of these proteins in the development and maintenance of normal electrical excitability in central neurons...
  19. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William Catterall; Fiscal Year: 1993
    ..Together, these experiments will provide important new information on the mechanisms used by central neurons to control the localization, cell surface density, and functional activity of sodium channels...
  20. MOLECULAR PROPERTIES OF VOLTAGE SENSITIVE CA++ CHANNELS
    William Catterall; Fiscal Year: 2003
    ..abstract_text> ..
  21. VOLTAGE SENSITIVE SODIUM CHANNELS IN BRAIN
    William Catterall; Fiscal Year: 2004
    ..These proposed studies will give new insight into the molecular mechanisms of sodium channel gating and its modification by second messenger-activated protein phosphorylation and by drugs and neurotoxins. ..
  22. VOLTAGE-SENSITIVE SODIUM CHANNELS IN BRAIN
    William Catterall; Fiscal Year: 1993
    ....