Scn2a

Summary

Gene Symbol: Scn2a
Description: sodium voltage-gated channel alpha subunit 2
Alias: NachII, Nav1.2, RII/RIIA, RNSCPIIR, SCN, Scn2a1, Scn2a2, ScpII, sodium channel protein type 2 subunit alpha, RIIA sodium channel protein, sodium channel protein type II subunit alpha, sodium channel protein, brain II subunit alpha, sodium channel voltage-gated type II alpha polypeptide, sodium channel, voltage-gated, type 2, alpha 1 polypeptide, sodium channel, voltage-gated, type 2, alpha 1 subunit, sodium channel, voltage-gated, type II, alpha 1, sodium channel, voltage-gated, type II, alpha subunit, voltage-gated sodium channel subunit alpha Nav1.2
Species: rat
Products:     Scn2a

Top Publications

  1. Mechaly I, Scamps F, Chabbert C, Sans A, Valmier J. Molecular diversity of voltage-gated sodium channel alpha subunits expressed in neuronal and non-neuronal excitable cells. Neuroscience. 2005;130:389-96 pubmed
  2. Plant L, Marks J, GOLDSTEIN S. SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons. elife. 2016;5: pubmed publisher
    ..Given the recognized role of INa in hypoxic brain damage, the SUMO pathway and NaV1.2 are identified as potential targets for neuroprotective interventions. ..
  3. Wildburger N, Ali S, Hsu W, Shavkunov A, Nenov M, Lichti C, et al. Quantitative proteomics reveals protein-protein interactions with fibroblast growth factor 12 as a component of the voltage-gated sodium channel 1.2 (nav1.2) macromolecular complex in Mammalian brain. Mol Cell Proteomics. 2015;14:1288-300 pubmed publisher
    ..Our studies will provide invaluable information to parse out the molecular determinant underlying neuronal excitability and plasticity, and extending the relevance of iFGFs signaling in the normal and diseased brain. ..
  4. Yu F, Westenbroek R, Silos Santiago I, McCormick K, Lawson D, Ge P, et al. Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci. 2003;23:7577-85 pubmed
    ..This novel, disulfide-linked beta subunit is likely to affect both protein-protein interactions and physiological function of multiple sodium channel alpha subunits. ..
  5. Ho W, Davis A, Chadha P, Greenwood I. Effective contractile response to voltage-gated Na+ channels revealed by a channel activator. Am J Physiol Cell Physiol. 2013;304:C739-47 pubmed publisher
    ..The TTX-sensitive Na(V)1.2 and Na(V)1.3 channels are likely involved in vascular control. ..
  6. Haufe V, Camacho J, Dumaine R, Günther B, Bollensdorff C, von Banchet G, et al. Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol. 2005;564:683-96 pubmed
    ..Our data suggest that neuronal and skeletal muscle Na(+) channels contribute to the action potential of cardiomyocytes in the adult mammalian heart. ..
  7. Noda M, Ikeda T, Kayano T, Suzuki H, Takeshima H, Kurasaki M, et al. Existence of distinct sodium channel messenger RNAs in rat brain. Nature. 1986;320:188-92 pubmed
    ..A partial DNA sequence complementary to a third homologous mRNA from rat brain has also been cloned...
  8. Ben Shalom R, Keeshen C, Berrios K, An J, Sanders S, Bender K. Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures. Biol Psychiatry. 2017;82:224-232 pubmed publisher
    Variants in the SCN2A gene that disrupt the encoded neuronal sodium channel NaV1.2 are important risk factors for autism spectrum disorder (ASD), developmental delay, and infantile seizures...
  9. Blankenship M, Coyle D, Baccei M. Transcriptional expression of voltage-gated Na? and voltage-independent K? channels in the developing rat superficial dorsal horn. Neuroscience. 2013;231:305-14 pubmed publisher

More Information

Publications44

  1. Scalmani P, Rusconi R, Armatura E, Zara F, Avanzini G, Franceschetti S, et al. Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel causing benign familial neonatal-infantile seizures. J Neurosci. 2006;26:10100-9 pubmed
    ..Thus, the pathogenic mechanism of BFNIS mutations is neuronal hyperexcitability caused by increased Na+ current. ..
  2. Sampo B, Tricaud N, Leveque C, Seagar M, Couraud F, Dargent B. Direct interaction between synaptotagmin and the intracellular loop I-II of neuronal voltage-sensitive sodium channels. Proc Natl Acad Sci U S A. 2000;97:3666-71 pubmed
    ..The Ca(2+)-regulated association between sodium channels and a protein implicated in vesicular fusion may have intriguing consequences for the establishment and regulation of neuronal excitability. ..
  3. Kalume F, Yu F, Westenbroek R, Scheuer T, Catterall W. Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice: implications for ataxia in severe myoclonic epilepsy in infancy. J Neurosci. 2007;27:11065-74 pubmed
    ..Loss of these channels in Purkinje neurons of mutant mice and SMEI patients may be sufficient to cause their ataxia and related functional deficits. ..
  4. Fort A, Cordaillat M, Thollon C, Salazar G, Mechaly I, Villeneuve N, et al. New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction. PLoS ONE. 2009;4:e7360 pubmed publisher
    ..2 isoform, together with the Na(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization. ..
  5. Gilchrist J, Das S, Van Petegem F, Bosmans F. Crystallographic insights into sodium-channel modulation by the ?4 subunit. Proc Natl Acad Sci U S A. 2013;110:E5016-24 pubmed publisher
  6. Jarnot M, Corbett A. Immunolocalization of NaV1.2 channel subtypes in rat and cat brain and spinal cord with high affinity antibodies. Brain Res. 2006;1107:1-12 pubmed
    ..Specific staining was limited to fibers located in the granule and molecular layer, in an orientation consistent with granule cell unmyelinated axon labeling. ..
  7. Striano P, Bordo L, Lispi M, Specchio N, Minetti C, Vigevano F, et al. A novel SCN2A mutation in family with benign familial infantile seizures. Epilepsia. 2006;47:218-20 pubmed
    ..Mutations in the voltage-gated sodium channel alpha2 subunit (SCN2A) gene on chromosome 2 were recently identified in families affected by neonatal and infantile seizures (benign ..
  8. Feldkamp M, Yu L, Shea M. Structural and energetic determinants of apo calmodulin binding to the IQ motif of the Na(V)1.2 voltage-dependent sodium channel. Structure. 2011;19:733-47 pubmed publisher
    ..Thermodynamic and structural studies of CaM-Na(v)1.2(IQp) interactions show that apo and (Ca(2+))(4)-CaM adopt distinct conformations that both permit tight association with Na(v)1.2(IQp) during gating. ..
  9. Sun L, Yan M, Hu X, Peng L, Che H, Bao Y, et al. MicroRNA-9 induces defective trafficking of Nav1.1 and Nav1.2 by targeting Navβ2 protein coding region in rat with chronic brain hypoperfusion. Mol Neurodegener. 2015;10:36 pubmed publisher
    ..1/Nav1.2 trafficking via targeting on Navβ2 protein in 2VO rats at post-transcriptional level, and inhibition of miR-9 may be a potentially valuable approach to prevent Nav1.1/Nav1.2 trafficking disturbance induced by CBH. ..
  10. Noda M, Numa S. Structure and function of sodium channel. J Recept Res. 1987;7:467-97 pubmed
    ..The transmembrane topology of the sodium channel molecule and the structure that may be involved in the voltage-dependent gating of the channel are discussed. ..
  11. Rougier J, van Bemmelen M, Bruce M, Jespersen T, Gavillet B, Apothéloz F, et al. Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins. Am J Physiol Cell Physiol. 2005;288:C692-701 pubmed
    ..This study shows that Nedd4-dependent ubiquitination of Na(v) channels may represent a general mechanism regulating the excitability of neurons and myocytes via modulation of channel density at the plasma membrane. ..
  12. Zhang M, Gajewiak J, Azam L, Bulaj G, Olivera B, Yoshikami D. Probing the Redox States of Sodium Channel Cysteines at the Binding Site of μO§-Conotoxin GVIIJ. Biochemistry. 2015;54:3911-20 pubmed publisher
    ..2[C918A], Cys910 is disulfide-bonded to Cys918 and Cys912, respectively. Redox states of extracellular cysteines of sodium channels have hitherto received scant attention, and further experiments with GVIIJ may help fill this void. ..
  13. Few W, Scheuer T, Catterall W. Dopamine modulation of neuronal Na(+) channels requires binding of A kinase-anchoring protein 15 and PKA by a modified leucine zipper motif. Proc Natl Acad Sci U S A. 2007;104:5187-92 pubmed
    ..Our results define the molecular mechanism by which G protein-coupled signaling pathways can rapidly and efficiently modulate neuronal excitability through local protein phosphorylation of Na(+) channels by specifically anchored PKA. ..
  14. Garrido J, Giraud P, Carlier E, Fernandes F, Moussif A, Fache M, et al. A targeting motif involved in sodium channel clustering at the axonal initial segment. Science. 2003;300:2091-4 pubmed
    ..Thus, this motif may play a fundamental role in controlling electrical excitability during development and plasticity. ..
  15. Hovey L, Fowler C, Mahling R, Lin Z, Miller M, Marx D, et al. Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2. Biophys Chem. 2017;224:1-19 pubmed publisher
    ..2 residues or auxiliary regulatory proteins interacting in the vicinity of the IQ motif. ..
  16. Berret E, Barron T, Xu J, Debner E, Kim E, Kim J. Oligodendroglial excitability mediated by glutamatergic inputs and Nav1.2 activation. Nat Commun. 2017;8:557 pubmed publisher
    ..2-driven action potentials, and that such process promotes myelination. ..
  17. Zhang M, McArthur J, Azam L, Bulaj G, Olivera B, French R, et al. Synergistic and antagonistic interactions between tetrodotoxin and mu-conotoxin in blocking voltage-gated sodium channels. Channels (Austin). 2009;3:32-8 pubmed
    ..The results lead us to postulate that in the bi-liganded NaV complex, TTX is bound between the peptide and the selectivity filter. These observations refine our view of Site 1 and open new possibilities in NaV pharmacology. ..
  18. 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. ..
  19. Griffiths M, Wang J, Joe B, Dracheva S, Kawahito Y, Shepard J, et al. Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen-induced arthritis. Arthritis Rheum. 2000;43:1278-89 pubmed
  20. Zhang J, Yarov Yarovoy V, Scheuer T, Karbat I, Cohen L, Gordon D, et al. Structure-function map of the receptor site for ?-scorpion toxins in domain II of voltage-gated sodium channels. J Biol Chem. 2011;286:33641-51 pubmed publisher
  21. Planells Cases R, Caprini M, Zhang J, Rockenstein E, Rivera R, Murre C, et al. Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice. Biophys J. 2000;78:2878-91 pubmed
    ..Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaChalpha(II). NaChalpha(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival. ..
  22. Zhang M, Han T, Olivera B, Bulaj G, Yoshikami D. ?-conotoxin KIIIA derivatives with divergent affinities versus efficacies in blocking voltage-gated sodium channels. Biochemistry. 2010;49:4804-12 pubmed publisher
  23. 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
  24. von Reyn C, Spaethling J, Mesfin M, Ma M, Neumar R, Smith D, et al. Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit. J Neurosci. 2009;29:10350-6 pubmed publisher
  25. Ptak K, Zummo G, Alheid G, Tkatch T, Surmeier D, McCrimmon D. Sodium currents in medullary neurons isolated from the pre-Bötzinger complex region. J Neurosci. 2005;25:5159-70 pubmed
    ..In the rostral ventral respiratory group (immediately caudal to preBötC), I(NaP) was also detected, but peak conductance, current density, and input resistance were smaller than in preBötC region cells. ..
  26. Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki Miyazaki E, et al. Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A. Epilepsy Res. 2002;48:15-23 pubmed
    ..The spectrum of GEFS+ should be expanded to include partial epilepsies and better to be termed autosomal dominant epilepsy with febrile seizures plus (ADEFS+). ..
  27. Maeda Y, Nakagawa T, Kuroda Y. Helix-stabilizing effects of the pentapeptide KIFMK and its related peptides on the sodium channel inactivation gate peptides. J Pept Res. 2001;58:413-23 pubmed
    ..It was concluded that the IFM motif and the two Lys residues are a prerequisite for effectively stabilizing the alpha-helix of MP-1A. ..
  28. Bosmans F, Milescu M, Swartz K. Palmitoylation influences the function and pharmacology of sodium channels. Proc Natl Acad Sci U S A. 2011;108:20213-8 pubmed publisher
    ..2a. Overall, our results demonstrate that lipid modifications are capable of altering the gating and pharmacological properties of rNav1.2a. ..
  29. Bouzidi M, Tricaud N, Giraud P, Kordeli E, Caillol G, Deleuze C, et al. Interaction of the Nav1.2a subunit of the voltage-dependent sodium channel with nodal ankyrinG. In vitro mapping of the interacting domains and association in synaptosomes. J Biol Chem. 2002;277:28996-9004 pubmed
    ..However, we could not find conditions that allowed for co-immunoprecipitation of ankyrin with the sodium channel beta(1) subunit. ..
  30. Kim H, DiBernardo A, Sloane J, Rasband M, Solomon D, Kosaras B, et al. WAVE1 is required for oligodendrocyte morphogenesis and normal CNS myelination. J Neurosci. 2006;26:5849-59 pubmed
    ..Together, these data demonstrate a role for WAVE1 in oligodendrocyte morphogenesis and myelination. ..
  31. Baek J, Rubinstein M, Scheuer T, Trimmer J. Reciprocal changes in phosphorylation and methylation of mammalian brain sodium channels in response to seizures. J Biol Chem. 2014;289:15363-73 pubmed publisher
    ..2 current. Reciprocal regulation of phosphorylation and MeArg of Nav1.2 may underlie changes in neuronal Nav channel function in response to seizures and also contribute to physiological modulation of neuronal excitability. ..
  32. Majumdar S, Sikdar S. Fast pseudo-periodic oscillation in the rat brain voltage-gated sodium channel alpha subunit. J Membr Biol. 2005;208:1-14 pubmed
  33. 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. ..
  34. Kjaergaard J. [Hospitals--new charge by physicians on equally worthy leadership]. Sygeplejersken. 1992;92:38-9 pubmed
  35. Schafer D, Custer A, Shrager P, Rasband M. Early events in node of Ranvier formation during myelination and remyelination in the PNS. Neuron Glia Biol. 2006;2:69-79 pubmed
    ..We suggest there is heterogeneity in the events leading to Nav channel clustering, indicating that multiple mechanisms might contribute to node of Ranvier formation in the PNS. ..