Scn8a

Summary

Gene Symbol: Scn8a
Description: sodium channel, voltage-gated, type VIII, alpha
Alias: AI853486, C630029C19Rik, NaCh6, Nav1.6, dmu, med, mnd-2, mnd2, nmf2, nmf335, nmf58, nur14, seal, sodium channel protein type 8 subunit alpha, ataxia 3, sodium channel protein type VIII subunit alpha, voltage-gated sodium channel Nav1.6 variant a, voltage-gated sodium channel Nav1.6 variant b, voltage-gated sodium channel alpha subunit, voltage-gated sodium channel subunit alpha Nav1.6
Species: mouse
Products:     Scn8a

Top Publications

  1. Van Wart A, Matthews G. Impaired firing and cell-specific compensation in neurons lacking nav1.6 sodium channels. J Neurosci. 2006;26:7172-80 pubmed
    ..6 underlies the transition to repetitive spiking in GCs. To test this possibility, we recorded from GCs of med (Na(v)1.6-null) and wild-type mice during postnatal development. By postnatal day 18, when the switch to Na(v)1...
  2. Shavkunov A, Wildburger N, Nenov M, James T, Buzhdygan T, Panova Elektronova N, et al. The fibroblast growth factor 14·voltage-gated sodium channel complex is a new target of glycogen synthase kinase 3 (GSK3). J Biol Chem. 2013;288:19370-85 pubmed publisher
  3. Duchen L, Stefani E. Electrophysiological studies of neuromuscular transmission in hereditary 'motor end-plate disease' of the mouse. J Physiol. 1971;212:535-48 pubmed
    ..7. The results suggest that the muscular weakness in this disease is due to the failure of nerve action potentials to invade motor nerve terminals so that muscle fibres become ;functionally denervated'. ..
  4. Cummins T, Dib Hajj S, Herzog R, Waxman S. Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons. FEBS Lett. 2005;579:2166-70 pubmed
    ..6 produce resurgent currents. These results demonstrate for the first time the intrinsic ability of Na(v)1.6 to produce a resurgent current, and also show that cell background is critical in permitting the generation of these currents. ..
  5. Raman I, Sprunger L, Meisler M, Bean B. Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. Neuron. 1997;19:881-91 pubmed
    ..action potentials were characterized in Purkinje neurons from ataxic mice lacking expression of the sodium channel Scn8a. Peak transient sodium current was approximately 60% of that in normal mice, but subthreshold sodium current was ..
  6. Osorio N, Cathala L, Meisler M, Crest M, Magistretti J, Delmas P. Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells. J Physiol. 2010;588:651-70 pubmed publisher
    ..expression of Nav subunits with recording of acute cerebellar slices from young and adult granule-specific Scn8a KO mice. Nav1.2 accumulated rapidly at early-formed axon initial segments (AISs). In contrast, Nav1...
  7. Levin S, Khaliq Z, Aman T, Grieco T, Kearney J, Raman I, et al. Impaired motor function in mice with cell-specific knockout of sodium channel Scn8a (NaV1.6) in cerebellar purkinje neurons and granule cells. J Neurophysiol. 2006;96:785-93 pubmed
    The Scn8a gene encodes the voltage-gated Na channel alpha subunit Na(V)1.6, which is widely expressed throughout the nervous system...
  8. Chen K, Sprunger L, Meisler M, Waller H, Godfrey D. Reduced spontaneous activity in the dorsal cochlear nucleus of Scn8a mutant mice. Brain Res. 1999;847:85-9 pubmed
    ..brain slices from mice homozygous for the med-J and jolting mutations in the neuronal sodium channel alpha-subunit Scn8a. Densities of spontaneously active neurons in slices from both mutants were significantly lower than in control ..
  9. Smith B, Côté P. Reduced Retinal Function in the Absence of Na(v)1.6. PLoS ONE. 2012;7:e31476 pubmed publisher
    Mice with a function-blocking mutation in the Scn8a gene that encodes Na(v)1...

More Information

Publications82

  1. Kohrman D, Plummer N, Schuster T, Jones J, Jang W, Burgess D, et al. Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15. Genomics. 1995;26:171-7 pubmed
    ..The transgene insertion site was mapped to distal chromosome 15 close to the locus motor endplate disease (med). The sequence of mouse DNA flanking the insertion site junctions was determined...
  2. Laezza F, Lampert A, Kozel M, Gerber B, Rush A, Nerbonne J, et al. FGF14 N-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels. Mol Cell Neurosci. 2009;42:90-101 pubmed publisher
    ..Thus, the FGF14 N-terminus is required for targeting and functional regulation of Nav channels, suggesting an important function for FGF14 alternative splicing in regulating neuronal excitability. ..
  3. Herzog R, Cummins T, Ghassemi F, Dib Hajj S, Waxman S. Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons. J Physiol. 2003;551:741-50 pubmed
    ..7 currents. Our results indicate that the firing properties of DRG neurons can be tuned by regulating expression of different sodium channel isoforms that have distinct repriming and closed-state inactivation kinetics. ..
  4. Martin M, Tang B, Papale L, Yu F, Catterall W, Escayg A. The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy. Hum Mol Genet. 2007;16:2892-9 pubmed
    ..sodium channel genes that are primarily expressed in the central nervous system: SCN1A, SCN2A, SCN3A and SCN8A. Mutations in SCN1A and SCN2A are responsible for several dominant idiopathic epilepsy disorders, including ..
  5. Levin S, Meisler M. Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (NaV1.6). Genesis. 2004;39:234-9 pubmed
    The sodium channel gene Scn8a encodes the channel NaV1.6, which is widely distributed in the central and peripheral nervous system. NaV1.6 is the major channel at the nodes of Ranvier in myelinated axons...
  6. Caldwell J, Schaller K, Lasher R, Peles E, Levinson S. Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc Natl Acad Sci U S A. 2000;97:5616-20 pubmed
    ..The specificity of this antibody was also demonstrated with the Na(v)1.6-deficient mouse mutant strain med, whose nodes were negative for Na(v)1.6 immunostaining...
  7. Do M, Bean B. Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice. J Neurophysiol. 2004;92:726-33 pubmed
    ..These results show that sodium channels other than Na(v)1.6 can make resurgent sodium current much like that from Na(v)1.6 channels. ..
  8. Buchner D, Seburn K, Frankel W, Meisler M. Three ENU-induced neurological mutations in the pore loop of sodium channel Scn8a (Na(v)1.6) and a genetically linked retinal mutation, rd13. Mamm Genome. 2004;15:344-51 pubmed
    ..Failure to complement a mutant allele of a positional candidate gene, Scn8a, demonstrated that the mutations are new alleles of Scn8a...
  9. Rush A, Dib Hajj S, Waxman S. Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones. J Physiol. 2005;564:803-15 pubmed
    ..6 and the Na(+)/Ca(2+) exchanger are colocalized, while selective expression of Na(v)1.2 may support action potential electrogenesis, at least at lower frequencies, while producing a smaller persistent current. ..
  10. Sharkey L, Cheng X, Drews V, Buchner D, Jones J, Justice M, et al. The ataxia3 mutation in the N-terminal cytoplasmic domain of sodium channel Na(v)1.6 disrupts intracellular trafficking. J Neurosci. 2009;29:2733-41 pubmed publisher
    ..Sequencing of the positional candidate gene Scn8a encoding the sodium channel Na(v)1...
  11. Jones J, Meisler M. Modeling human epilepsy by TALEN targeting of mouse sodium channel Scn8a. Genesis. 2014;52:141-8 pubmed publisher
    To evaluate the efficiency of TALEN technology for introducing mutations into the mouse genome we targeted Scn8a, a member of a multigene family with nine closely related paralogs...
  12. Koay G, Heffner R, Heffner H. Behavioral audiograms of homozygous med(J) mutant mice with sodium channel deficiency and unaffected controls. Hear Res. 2002;171:111-118 pubmed
    ..The med(J) mutation results in greatly reduced levels of Scn8a voltage-gated sodium channels, which causes abnormal conduction of action potentials throughout the nervous system ..
  13. Hossain W, Antic S, Yang Y, Rasband M, Morest D. Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea. J Neurosci. 2005;25:6857-68 pubmed
  14. De Repentigny Y, Côté P, Pool M, Bernier G, Girard S, Vidal S, et al. Pathological and genetic analysis of the degenerating muscle (dmu) mouse: a new allele of Scn8a. Hum Mol Genet. 2001;10:1819-27 pubmed
    ..Initial analysis of candidate genes on mouse chromosome 15 reveal that although intact transcripts for Scn8a, the gene encoding the sodium channel 8a subunit, are present in dmu mice, their levels are dramatically reduced...
  15. Chen Y, Yu F, Sharp E, Beacham D, Scheuer T, Catterall W. Functional properties and differential neuromodulation of Na(v)1.6 channels. Mol Cell Neurosci. 2008;38:607-15 pubmed publisher
    ..The unique properties of Na(V)1.6 channels, together with the resurgent currents that they conduct in neurons, make these channels well-suited to provide the driving force for sustained repetitive firing, a crucial property of neurons. ..
  16. McKinney B, Chow C, Meisler M, Murphy G. Exaggerated emotional behavior in mice heterozygous null for the sodium channel Scn8a (Nav1.6). Genes Brain Behav. 2008;7:629-38 pubmed publisher
    The Scn8a gene encodes the alpha-subunit of Na(v)1.6, a neuronal voltage-gated sodium channel. Mice homozygous for mutations in the Scn8a gene exhibit motor impairments...
  17. Sprunger L, Escayg A, Tallaksen Greene S, Albin R, Meisler M. Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3. Hum Mol Genet. 1999;8:471-9 pubmed
    The mouse mutant medJ contains a splice site mutation in the neuronal sodium channel Scn8a that results in a very low level of expression...
  18. Vega A, Henry D, Matthews G. Reduced expression of Na(v)1.6 sodium channels and compensation by Na(v)1.2 channels in mice heterozygous for a null mutation in Scn8a. Neurosci Lett. 2008;442:69-73 pubmed publisher
    The voltage-gated sodium channel alpha subunit Na(v)1.6, encoded by the Scn8a gene, accumulates at high density at mature nodes of Ranvier of myelinated axons, replacing the Na(v)1.2 channels found at nodes earlier in development...
  19. Kohrman D, Harris J, Meisler M. Mutation detection in the med and medJ alleles of the sodium channel Scn8a. Unusual splicing due to a minor class AT-AC intron. J Biol Chem. 1996;271:17576-81 pubmed
    ..mutation at the mouse med locus led to the identification of the novel voltage-gated sodium channel gene Scn8a (Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., and Meisler, M. H.(1995) Nat...
  20. Garcia K, Sprunger L, Meisler M, Beam K. The sodium channel Scn8a is the major contributor to the postnatal developmental increase of sodium current density in spinal motoneurons. J Neurosci. 1998;18:5234-9 pubmed
    ..For mice lacking a functional Scn8a sodium channel gene, motoneuronal sodium current density was comparable at P0 to that of normal mice but failed to ..
  21. Hawkins N, Martin M, Frankel W, Kearney J, Escayg A. Neuronal voltage-gated ion channels are genetic modifiers of generalized epilepsy with febrile seizures plus. Neurobiol Dis. 2011;41:655-60 pubmed publisher
    ..we used mouse models to study the effect of combining the human GEFS+ mutation SCN1A-R1648H with SCN2A, KCNQ2, and SCN8A mutations...
  22. Kohrman D, Smith M, Goldin A, Harris J, Meisler M. A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting. J Neurosci. 1996;16:5993-9 pubmed
    The voltage-gated sodium channel Scn8a is broadly distributed in brain and spinal cord...
  23. O Brien J, Sharkey L, Vallianatos C, Han C, Blossom J, Yu T, et al. Interaction of voltage-gated sodium channel Nav1.6 (SCN8A) with microtubule-associated protein Map1b. J Biol Chem. 2012;287:18459-66 pubmed publisher
    ..Mutation of the Map1b binding site of Na(v)1.6 prevented generation of sodium current in transfected cells. The data indicate that Map1b facilitates trafficking of Na(v)1.6 to the neuronal cell surface. ..
  24. Dick D, Boakes R, Harris J. A cerebellar abnormality in the mouse with motor end-plate disease. Neuropathol Appl Neurobiol. 1985;11:141-7 pubmed
    The murine mutant with motor end-plate disease (med) exhibits a progressive weakness which is due to a functional denervation of skeletal muscle. It is inherited as an autosomal recessive trait and has two alleles...
  25. Côté P, De Repentigny Y, Coupland S, Schwab Y, Roux M, Levinson S, et al. Physiological maturation of photoreceptors depends on the voltage-gated sodium channel NaV1.6 (Scn8a). J Neurosci. 2005;25:5046-50 pubmed
    ..The functional deficit was not associated with any morphological abnormality. We demonstrate that Scn8a is expressed in the ganglion and inner nuclear layers and at low levels in the outer nuclear layer beginning ..
  26. Burgess D, Kohrman D, Galt J, Plummer N, Jones J, Spear B, et al. Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'. Nat Genet. 1995;10:461-5 pubmed
    ..We have isolated a voltage-gated sodium channel gene, Scn8a, from the flanking region of a transgene-induced allele of med...
  27. Papale L, Beyer B, Jones J, Sharkey L, Tufik S, Epstein M, et al. Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice. Hum Mol Genet. 2009;18:1633-41 pubmed publisher
    In a chemical mutagenesis screen, we identified the novel Scn8a(8J) allele of the gene encoding the neuronal voltage-gated sodium channel Na(v)1.6...
  28. Kearney J, Buchner D, De Haan G, Adamska M, Levin S, Furay A, et al. Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Na(v)1.6). Hum Mol Genet. 2002;11:2765-75 pubmed
    b>Scn8a encodes an abundant, widely distributed voltage-gated sodium channel found throughout the central and peripheral nervous systems...
  29. Herzog R, Liu C, Waxman S, Cummins T. Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties. J Neurosci. 2003;23:8261-70 pubmed
  30. Lee Y, Smith R, Jordan W, King B, Won J, Valpuesta J, et al. Prefoldin 5 is required for normal sensory and neuronal development in a murine model. J Biol Chem. 2011;286:726-36 pubmed publisher
    ..The diversity of phenotypes demonstrated by models carrying mutations in different PFDN subunits suggests that each PFDN subunit must confer a distinct substrate specificity to the prefoldin holocomplex. ..
  31. Priatel J, Sarkar M, Schachter H, Marth J. Isolation, characterization and inactivation of the mouse Mgat3 gene: the bisecting N-acetylglucosamine in asparagine-linked oligosaccharides appears dispensable for viability and reproduction. Glycobiology. 1997;7:45-56 pubmed
    ..fluorescence in situ hybridization (FISH), the Mgat3 gene was regionally mapped to chromosome 15E11, near the Scn8a sodium channel gene at 15F1...
  32. Smith M, Smith R, Plummer N, Meisler M, Goldin A. Functional analysis of the mouse Scn8a sodium channel. J Neurosci. 1998;18:6093-102 pubmed
    The mouse Scn8a sodium channel and its ortholog Na6 in the rat are abundantly expressed in the CNS. Mutations in mouse Scn8a result in neurological disorders, including paralysis, ataxia, and dystonia...
  33. Jones J, Ranscht B, Berglund E, Gruenheid S, Gros P, Meisler M. Close linkage of three neuronal genes on distal mouse chromosome 15. Mamm Genome. 1996;7:696-7 pubmed
  34. Lopez Santiago L, Meadows L, Ernst S, Chen C, Malhotra J, McEwen D, et al. Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol. 2007;43:636-47 pubmed
    ..Together, these results suggest that beta1 is critical for normal cardiac excitability and loss of beta1 may be associated with a long QT phenotype. ..
  35. Kile B, Hentges K, Clark A, Nakamura H, Salinger A, Liu B, et al. Functional genetic analysis of mouse chromosome 11. Nature. 2003;425:81-6 pubmed
    ..The mutations reveal new defects in haematopoiesis, craniofacial and cardiovascular development, and fertility. ..
  36. Shrager P, Youngman M. Preferential conduction block of myelinated axons by nitric oxide. J Neurosci Res. 2017;95:1402-1414 pubmed publisher
    ..It was concluded that NO likely interacts with axonal Na+ channels through an intermediate that is associated with myelin. © 2016 Wiley Periodicals, Inc. ..
  37. Sato T, Fujita M, Shimizu Y, Kanetaka H, Chu L, Côté P, et al. Glial reaction in the spinal cord of the degenerating muscle mouse (Scn8a (dmu)). Neurochem Res. 2015;40:124-9 pubmed publisher
    ..of the degenerating muscle (dmu) mouse, which harbours a null mutation in the voltage-gated sodium channel gene Scn8a and does not produce functional Nav1.6 channel...
  38. Dover K, Solinas S, D Angelo E, Goldfarb M. Long-term inactivation particle for voltage-gated sodium channels. J Physiol. 2010;588:3695-711 pubmed publisher
    ..We discuss potential structural mechanisms of long-term inactivation and potential roles of A-type FHFs in the modulation of action potential generation and conduction. ..
  39. Makinson C, Tanaka B, Lamar T, Goldin A, Escayg A. Role of the hippocampus in Nav1.6 (Scn8a) mediated seizure resistance. Neurobiol Dis. 2014;68:16-25 pubmed publisher
    ..Mutations that reduce the activity of the mouse Scn8a gene, in contrast, are found to confer seizure resistance and extend the lifespan of mouse models of DS and GEFS+...
  40. Wang J, Lin W, Morris T, Banderali U, Juranka P, Morris C. Membrane trauma and Na+ leak from Nav1.6 channels. Am J Physiol Cell Physiol. 2009;297:C823-34 pubmed publisher
    ..When, during head trauma, nodes experienced bleb-inducing membrane damage of varying intensities, nodal Nav1.6 channels should immediately "leak" over a broadly left-smeared window current range. ..
  41. Rieger F, Pincon Raymond M, Lombet A, Ponzio G, Lazdunski M, Sidman R. Paranodal dysmyelination and increase in tetrodotoxin binding sites in the sciatic nerve of the motor end-plate disease (med/med) mouse during postnatal development. Dev Biol. 1984;101:401-9 pubmed
    Motor end-plate disease (med), in the mouse, is a hereditary neuromuscular defect, caused by a single gene mutation and characterized by a progressive muscle weakness...
  42. Hao M, Lomax A, McKeown S, Reid C, Young H, Bornstein J. Early development of electrical excitability in the mouse enteric nervous system. J Neurosci. 2012;32:10949-60 pubmed publisher
    ..Spontaneous depolarizations resembling excitatory postsynaptic potentials were observed at E12.5. The ENS is one of the earliest parts of the developing nervous system to exhibit mature forms of electrical activity. ..
  43. Caillol G, Vacher H, Musarella M, Bellouze S, Dargent B, Autillo Touati A. Motor endplate disease affects neuromuscular junction maturation. Eur J Neurosci. 2012;36:2400-8 pubmed publisher
    ..In motor endplate disease (med) mice, neuromuscular transmission is severely impaired without alteration of axonal conduction and a lethal ..
  44. Grieco T, Afshari F, Raman I. A role for phosphorylation in the maintenance of resurgent sodium current in cerebellar purkinje neurons. J Neurosci. 2002;22:3100-7 pubmed
    ..Together, the results suggest that constitutive phosphorylation of the sodium channel complex of Purkinje neurons is necessary to maintain a functional blocking element and produce resurgent sodium current. ..
  45. Hain H, Crabbe J, Bergeson S, Belknap J. Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains. J Pharmacol Exp Ther. 2000;293:180-7 pubmed
    ..0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males. ..
  46. Jones J, Dionne L, Dell Orco J, Parent R, Krueger J, Cheng X, et al. Single amino acid deletion in transmembrane segment D4S6 of sodium channel Scn8a (Nav1.6) in a mouse mutant with a chronic movement disorder. Neurobiol Dis. 2016;89:36-45 pubmed publisher
    Mutations of the neuronal sodium channel gene SCN8A are associated with lethal movement disorders in the mouse and with human epileptic encephalopathy...
  47. Yang W, Mansour S. Expression and genetic analysis of prtb, a gene that encodes a highly conserved proline-rich protein expressed in the brain. Dev Dyn. 1999;215:108-16 pubmed
    ..This could be due to functional redundancy as Northern blot hybridization analysis clearly demonstrated that prtb(gt) is likely to be a null allele. ..
  48. Hassen G, Feliberti J, Kesner L, Stracher A, Mokhtarian F. Prevention of axonal injury using calpain inhibitor in chronic progressive experimental autoimmune encephalomyelitis. Brain Res. 2008;1236:206-15 pubmed publisher
    ..Thus, this novel drug, which markedly suppresses the disease course, axonal injury and its progression, is a candidate for the treatment of a neurodegenerative disease such as multiple sclerosis. ..
  49. Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci. 2007;27:5903-14 pubmed
    ..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. ..
  50. Gasser A, Cheng X, Gilmore E, Tyrrell L, Waxman S, Dib Hajj S. Two Nedd4-binding motifs underlie modulation of sodium channel Nav1.6 by p38 MAPK. J Biol Chem. 2010;285:26149-61 pubmed publisher
    ..We report here that p38 activation in hippocampal neurons from wild-type mice, but not from Scn8a(medtg) mice that lack Na(v)1...
  51. Pal D, Jones J, Wisidagamage S, Meisler M, Mashour G. Reduced Nav1.6 Sodium Channel Activity in Mice Increases In Vivo Sensitivity to Volatile Anesthetics. PLoS ONE. 2015;10:e0134960 pubmed publisher
    ..This is the first report linking reduced activity of a specific voltage-gated sodium channel to increased sensitivity to general anesthetics in vivo. ..
  52. Komada M, Soriano P. [Beta]IV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J Cell Biol. 2002;156:337-48 pubmed
    ..These results indicate that betaIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR. ..
  53. Swensen A, Bean B. Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance. J Neurosci. 2005;25:3509-20 pubmed
    ..6-/- mutant neurons. Thus, Purkinje neurons have both acute and long-term feedback mechanisms that serve to maintain burst firing when voltage-dependent sodium conductance is reduced. ..
  54. Yin L, Rasch M, He Q, Wu S, Dou F, Shu Y. Selective Modulation of Axonal Sodium Channel Subtypes by 5-HT1A Receptor in Cortical Pyramidal Neuron. Cereb Cortex. 2017;27:509-521 pubmed publisher
  55. Huang X, Du Y, Yang P, Lin S, Xi Y, Yang Z, et al. Age-dependent alterations of voltage-gated Na(+) channel isoforms in rat sinoatrial node. Mech Ageing Dev. 2015;152:80-90 pubmed publisher
    ..1, Nav1.6, Navβ1 and Navβ3 mRNA and their reduced levels in rat SAN during aging. These results indicated an age-dependent alterations in expression and relative function of NaCh in rat SAN. ..
  56. Papale L, Paul K, Sawyer N, Manns J, Tufik S, Escayg A. Dysfunction of the Scn8a voltage-gated sodium channel alters sleep architecture, reduces diurnal corticosterone levels, and enhances spatial memory. J Biol Chem. 2010;285:16553-61 pubmed publisher
    ..A null mutation in the VGSC gene SCN8A, which encodes the transmembrane protein Na(v)1.6, was identified previously in a human family...
  57. Malhotra J, Thyagarajan V, Chen C, Isom L. Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem. 2004;279:40748-54 pubmed
    ..5 and pYbeta1 and that these complexes are in close association with both N-cadherin and connexin-43. beta1 phosphorylation appears to regulate its localization to differential subcellular domains. ..
  58. Kopmels B, Wollman E, Guastavino J, Delhaye Bouchaud N, Fradelizi D, Mariani J. Interleukin-1 hyperproduction by in vitro activated peripheral macrophages from cerebellar mutant mice. J Neurochem. 1990;55:1980-5 pubmed
    ..These observations establish that in several point mutations in mice, central nervous degeneration is associated with dysregulation of IL-1 production by peripheral macrophages. ..
  59. Brackenbury W, Calhoun J, Chen C, Miyazaki H, Nukina N, Oyama F, et al. Functional reciprocity between Na+ channel Nav1.6 and beta1 subunits in the coordinated regulation of excitability and neurite outgrowth. Proc Natl Acad Sci U S A. 2010;107:2283-8 pubmed publisher
    ..6 localization and consequent high-frequency firing require beta1. We conclude that VGSC subunits function in macromolecular signaling complexes regulating both neuronal excitability and migration during cerebellar development. ..
  60. Porter J, Goldstein L, Kasarskis E, Brueckner J, Spear B. The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units. Exp Neurol. 1996;139:328-34 pubmed
    ..locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a. We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(..
  61. Crabtree G, Sun Z, Kvajo M, Broek J, Fenelon K, McKellar H, et al. Alteration of Neuronal Excitability and Short-Term Synaptic Plasticity in the Prefrontal Cortex of a Mouse Model of Mental Illness. J Neurosci. 2017;37:4158-4180 pubmed publisher
  62. Southwood C, He C, Garbern J, Kamholz J, Arroyo E, Gow A. CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. J Neurosci. 2004;24:11215-25 pubmed
  63. Xiao M, Bosch M, Nerbonne J, Ornitz D. FGF14 localization and organization of the axon initial segment. Mol Cell Neurosci. 2013;56:393-403 pubmed publisher
    ..In (Scn8a(med)) mice, which are deficient in expression of the Nav1...
  64. Brocard C, Plantier V, Boulenguez P, Liabeuf S, Bouhadfane M, Viallat Lieutaud A, et al. Cleavage of Na(+) channels by calpain increases persistent Na(+) current and promotes spasticity after spinal cord injury. Nat Med. 2016;22:404-11 pubmed publisher
    ..This study demonstrates that Nav channel expression in lumbar motoneurons is altered after SCI, and it shows a tight relationship between the calpain-dependent proteolysis of Nav1.6 channels, the upregulation of I(NaP) and spasticity. ..
  65. Füchtbauer E. Nerve transplantation shows that motor end-plate disease is not a primary Schwann cell defect. Exp Neurol. 1987;97:135-42 pubmed
    Motor end-plate diseased (MED) mice have altered nerve impulse conduction velocities and refractory periods...
  66. Vega A, Avila G, Matthews G. Interaction between the transcriptional corepressor Sin3B and voltage-gated sodium channels modulates functional channel expression. Sci Rep. 2013;3:2809 pubmed publisher
  67. Baloh R, Strickland A, Ryu E, Le N, Fahrner T, Yang M, et al. Congenital hypomyelinating neuropathy with lethal conduction failure in mice carrying the Egr2 I268N mutation. J Neurosci. 2009;29:2312-21 pubmed publisher
  68. Guloglu F, Smith B, Roman C. Multiple levels of selection responsive to immunoglobulin light chain and heavy chain structures impede the development of Dmu-expressing B cells. J Immunol. 2008;181:4098-106 pubmed
    The truncated/V(H)-less mouse H chain Dmu forms precursor B cell receptors with the surrogate L chain complex that promotes allelic exclusion but not other aspects of pre-B cell development, causing most progenitor B cells expressing ..
  69. Hsu W, Nenov M, Shavkunov A, Panova N, Zhan M, Laezza F. Identifying a kinase network regulating FGF14:Nav1.6 complex assembly using split-luciferase complementation. PLoS ONE. 2015;10:e0117246 pubmed publisher
  70. Zhu H, Shibata A, Inai T, Nomura M, Shibata Y, Brock J, et al. Characterization of NaV1.6-mediated Na+ currents in smooth muscle cells isolated from mouse vas deferens. J Cell Physiol. 2010;223:234-43 pubmed publisher
    ..6-null mice (Na(V)1.6(-/-)) lacking the expression of the Na(+) channel gene, Scn8a, and their wild-type littermates (Na(V)1.6(+/+)). Immunohistochemistry confirmed expression of Na(V)1...
  71. Buchner D, Trudeau M, Meisler M. SCNM1, a putative RNA splicing factor that modifies disease severity in mice. Science. 2003;301:967-9 pubmed
    ..The primary mutation (medJ) changes a splice donor site of the sodium channel gene Scn8a (Nav1.6)...
  72. Liu C, Tan F, Xiao Z, Dawe G. Amyloid precursor protein enhances Nav1.6 sodium channel cell surface expression. J Biol Chem. 2015;290:12048-57 pubmed publisher
    ..Phosphorylation of APP695 at Thr-668 enhanced its interaction with Nav1.6. Therefore, we show that APP enhances Nav1.6 sodium channel cell surface expression through a Go-coupled JNK pathway. ..
  73. Sprissler R, Wagnon J, Bunton Stasyshyn R, Meisler M, Hammer M. Altered gene expression profile in a mouse model of SCN8A encephalopathy. Exp Neurol. 2017;288:134-141 pubmed publisher
    b>SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6...