Scn9a

Summary

Gene Symbol: Scn9a
Description: sodium channel, voltage-gated, type IX, alpha
Alias: Nav1.7, PN1, mKIAA4197, sodium channel protein type 9 subunit alpha, peripheral sodium channel 1, sodium channel 25, sodium channel, voltage-gated, type IX, alpha polypeptide, voltage-gated sodium channel Nav1.7 variant a, voltage-gated sodium channel Nav1.7 variant b, voltage-gated sodium channel alpha subunit Nav1.7
Species: mouse
Products:     Scn9a

Top Publications

  1. Shields S, Cheng X, Uceyler N, Sommer C, Dib Hajj S, Waxman S. Sodium channel Na(v)1.7 is essential for lowering heat pain threshold after burn injury. J Neurosci. 2012;32:10819-32 pubmed publisher
    ..Our results offer insights into the molecular and cellular mechanisms of modality-specific pain signaling, and suggest Na(v)1.7-blocking drugs may be effective in burn patients. ..
  2. Minett M, Nassar M, Clark A, Passmore G, Dickenson A, Wang F, et al. Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons. Nat Commun. 2012;3:791 pubmed publisher
    ..Ablating Nav1.7 gene (SCN9A) expression in all sensory neurons using Advillin-Cre abolishes mechanical pain, inflammatory pain and reflex ..
  3. Singh N, Pappas C, Dahle E, Claes L, Pruess T, De Jonghe P, et al. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. PLoS Genet. 2009;5:e1000649 pubmed publisher
    ..large Utah family with significant linkage to chromosome 2q24 led us to identify a new febrile seizure (FS) gene, SCN9A encoding Na(v)1.7. In 21 affected members, we uncovered a potential mutation in a highly conserved amino acid, p...
  4. Nassar M, Stirling L, Forlani G, Baker M, Matthews E, Dickenson A, et al. Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci U S A. 2004;101:12706-11 pubmed
    ..A congenital pain syndrome in humans recently has been mapped to the Na(v)1.7 gene, SCN9A. Dominant Na(v)1...
  5. Eijkelkamp N, Linley J, Torres J, Bee L, Dickenson A, Gringhuis M, et al. A role for Piezo2 in EPAC1-dependent mechanical allodynia. Nat Commun. 2013;4:1682 pubmed publisher
    ..These data indicate that the Epac1-Piezo2 axis has a role in the development of mechanical allodynia during neuropathic pain. ..
  6. Weiss J, Pyrski M, Jacobi E, Bufe B, Willnecker V, Schick B, et al. Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature. 2011;472:186-90 pubmed publisher
    Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1...
  7. Abrahamsen B, Zhao J, Asante C, Cendan C, Marsh S, Martinez Barbera J, et al. The cell and molecular basis of mechanical, cold, and inflammatory pain. Science. 2008;321:702-5 pubmed publisher
    ..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. ..
  8. Nassar M, Levato A, Stirling L, Wood J. Neuropathic pain develops normally in mice lacking both Na(v)1.7 and Na(v)1.8. Mol Pain. 2005;1:24 pubmed
    ..7 in determining inflammatory pain thresholds, the development of neuropathic pain does not require the presence of either Nav1.7 or Nav1.8 alone or in combination. ..
  9. Minett M, Falk S, Santana Varela S, Bogdanov Y, Nassar M, Heegaard A, et al. Pain without nociceptors? Nav1.7-independent pain mechanisms. Cell Rep. 2014;6:301-12 pubmed publisher
    ..8-positive nociceptors. Thus, similar pain phenotypes arise through distinct cellular and molecular mechanisms. Therefore, rational analgesic drug therapy requires patient stratification in terms of mechanisms and not just phenotype. ..

More Information

Publications39

  1. Raouf R, Rugiero F, Kiesewetter H, Hatch R, Hummler E, Nassar M, et al. Sodium channels and mammalian sensory mechanotransduction. Mol Pain. 2012;8:21 pubmed publisher
    ..DEG/ENaC sodium channels are not mechanosensors in mouse sensory neurons. ..
  2. Ren A, Wang K, Zhang H, Liu A, Ma X, Liang Q, et al. ZBTB20 regulates nociception and pain sensation by modulating TRP channel expression in nociceptive sensory neurons. Nat Commun. 2014;5:4984 pubmed publisher
    ..Our findings point to ZBTB20 as a critical regulator of nociception and pain sensation by modulating TRP channels expression in nociceptors. ..
  3. Fotia A, Ekberg J, Adams D, Cook D, Poronnik P, Kumar S. Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem. 2004;279:28930-5 pubmed
    ..Interestingly, Nedd4 suppressed the activity of Na(v)1.2 and Na(v)1.7 but was a poor inhibitor of Na(v)1.8. Our results provide evidence that Nedd4 and Nedd4-2 are likely to be key regulators of specific neuronal Na(v) channels in vivo. ..
  4. Yang S, Xiao Y, Kang D, Liu J, Li Y, Undheim E, et al. Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc Natl Acad Sci U S A. 2013;110:17534-9 pubmed publisher
    ..This study establishes µ-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting NaV1.7, which might be suitable for treating a wide range of human pain pathologies. ..
  5. Tsunozaki M, Lennertz R, Vilceanu D, Katta S, Stucky C, Bautista D. A 'toothache tree' alkylamide inhibits A? mechanonociceptors to alleviate mechanical pain. J Physiol. 2013;591:3325-40 pubmed publisher
    ..These results suggest that sanshool targets voltage-gated sodium channels on A? mechanosensory nociceptors to dampen excitability and thus induce 'fast pain' analgesia. ..
  6. Zhang Q, Chibalina M, Bengtsson M, Groschner L, Ramracheya R, Rorsman N, et al. Na+ current properties in islet α- and β-cells reflect cell-specific Scn3a and Scn9a expression. J Physiol. 2014;592:4677-96 pubmed publisher
    ..Single-cell PCR analyses show that both α- and β-cells have Nav1.3 (Scn3) and Nav1.7 (Scn9a) α subunits, but their relative proportions differ: β-cells principally express Nav1.7 and α-cells Nav1.3...
  7. Ahn H, Black J, Zhao P, Tyrrell L, Waxman S, Dib Hajj S. Nav1.7 is the predominant sodium channel in rodent olfactory sensory neurons. Mol Pain. 2011;7:32 pubmed publisher
    ..Homozygous or compound heterozygous loss-of-function mutations in SCN9A, the gene which encodes Nav1.7, cause congenital insensitivity to pain (CIP) accompanied by anosmia...
  8. Minett M, Pereira V, Sikandar S, Matsuyama A, Lolignier S, Kanellopoulos A, et al. Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7. Nat Commun. 2015;6:8967 pubmed publisher
    Loss-of-function mutations in the SCN9A gene encoding voltage-gated sodium channel Nav1.7 cause congenital insensitivity to pain in humans and mice. Surprisingly, many potent selective antagonists of Nav1.7 are weak analgesics...
  9. Castillo S, Xiao Q, Lyu M, Kozak C, Nikodem V. Organization, sequence, chromosomal localization, and promoter identification of the mouse orphan nuclear receptor Nurr1 gene. Genomics. 1997;41:250-7 pubmed
    ..These data help to explain the different response characteristics of two closely related early response genes, Nurr1 and Nur77. ..
  10. Branco T, Tozer A, Magnus C, Sugino K, Tanaka S, Lee A, et al. Near-Perfect Synaptic Integration by Nav1.7 in Hypothalamic Neurons Regulates Body Weight. Cell. 2016;165:1749-1761 pubmed publisher
    ..This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration...
  11. Kanellopoulos A, Koenig J, Huang H, Pyrski M, Millet Q, Lolignier S, et al. Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene-targeted mice. EMBO J. 2018;37:427-445 pubmed publisher
    ..7 and opioid signalling. Further information on physiological interactions provided with this normal epitope-tagged mouse should provide useful insights into the many functions now associated with the NaV1.7 channel. ..
  12. Eom T, Zhang C, Wang H, Lay K, Fak J, Noebels J, et al. NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure. elife. 2013;2:e00178 pubmed publisher
    ..The data reveal a hidden means of dynamic RNA regulation linking electrical activity to splicing and protein output, and of mediating homeostatic excitation/inhibition balance in neurons.DOI:http://dx.doi.org/10.7554/eLife.00178.001. ..
  13. Mollah M, Ishikawa A. Intersubspecific subcongenic mouse strain analysis reveals closely linked QTLs with opposite effects on body weight. Mamm Genome. 2011;22:282-9 pubmed publisher
    ..These findings illustrate the complex genetic nature of body weight regulation and support the importance of subcongenic mouse analysis to dissect closely linked loci. ..
  14. McCormack K, Santos S, Chapman M, Krafte D, Marron B, West C, et al. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels. Proc Natl Acad Sci U S A. 2013;110:E2724-32 pubmed publisher
    ..The present study provides a potential framework for identifying subtype selective small molecule sodium channel inhibitors targeting interaction sites away from the pore region. ..
  15. Yamane M, Yamashita N, Hida T, Kamiya Y, Nakamura F, Kolattukudy P, et al. A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling. J Cell Sci. 2017;130:1393-1403 pubmed publisher
    ..We here demonstrate that Nav1.7 (encoded by SCN9A), a TTX-sensitive Na+ channel, by coupling with collapsin response mediator protein 1 (CRMP1), ..
  16. Minett M, Eijkelkamp N, Wood J. Significant determinants of mouse pain behaviour. PLoS ONE. 2014;9:e104458 pubmed publisher
    ..Failure to conduct behavioural tests at different anatomical locations, stimulus intensities, and at different points in the circadian cycle may lead to a pain behavioural phenotype being misinterpreted, or missed altogether. ..
  17. Beckers M, Ernst E, Belcher S, Howe J, Levenson R, Gros P. A new sodium channel alpha-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2. Genomics. 1996;36:202-5 pubmed
    ..location of a newly identified gene encoding an alpha-subunit isoform of the sodium channel from Schwann cells, Scn9a. Linkage analysis established that Scn9a mapped to the proximal segment of mouse chromosome 2...
  18. Yang L, Dong F, Yang Q, Yang P, Wu R, Wu Q, et al. FGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7. Neuron. 2017;93:806-821.e9 pubmed publisher
    ..7 interaction reduced the heat-evoked action potential firing and nociceptive behavior. Thus, beyond the thermosensors, the FGF13/Nav1.7 complex is essential for sustaining the transmission of noxious heat signals. ..
  19. Huang J, Yang Y, Dib Hajj S, van Es M, Zhao P, Salomon J, et al. Depolarized inactivation overcomes impaired activation to produce DRG neuron hyperexcitability in a Nav1.7 mutation in a patient with distal limb pain. J Neurosci. 2014;34:12328-40 pubmed publisher
    Sodium channel Nav1.7, encoded by SCN9A, is expressed in DRG neurons and regulates their excitability. Genetic and functional studies have established a critical contribution of Nav1.7 to human pain disorders...
  20. 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. ..
  21. Hodgdon K, Hingtgen C, Nicol G. Dorsal root ganglia isolated from Nf1+/- mice exhibit increased levels of mRNA expression of voltage-dependent sodium channels. Neuroscience. 2012;206:237-44 pubmed publisher
  22. Rush A, Craner M, Kageyama T, Dib Hajj S, Waxman S, Ranscht B. Contactin regulates the current density and axonal expression of tetrodotoxin-resistant but not tetrodotoxin-sensitive sodium channels in DRG neurons. Eur J Neurosci. 2005;22:39-49 pubmed
  23. Kozak C, Sangameswaran L. Genetic mapping of the peripheral sodium channel genes, Scn9a and Scn10a, in the mouse. Mamm Genome. 1996;7:787-8 pubmed
  24. Eisenried A, Klukinov M, Yeomans D, Tzabazis A. Antihyperalgesic effect by herpes vector-mediated knockdown of NaV1.7 sodium channels after skin incision. Neuroreport. 2017;28:661-665 pubmed publisher
    ..This then, in turn, provides presumptive support to the hypothesis that overexpression of the NaV1.7 channel is an important mechanism underlying hyperalgesia and allodynia following skin incision. ..
  25. Gingras J, Smith S, Matson D, Johnson D, Nye K, Couture L, et al. Global Nav1.7 knockout mice recapitulate the phenotype of human congenital indifference to pain. PLoS ONE. 2014;9:e105895 pubmed publisher
    ..7-targeted therapeutics. Results further suggest that Nav1.7 may retain its key role in persistent as well as acute forms of pain. ..
  26. Gao N, Lu M, Echeverri F, Laita B, Kalabat D, Williams M, et al. Voltage-gated sodium channels in taste bud cells. BMC Neurosci. 2009;10:20 pubmed publisher
    ..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...
  27. Isensee J, Krahé L, Moeller K, Pereira V, Sexton J, Sun X, et al. Synergistic regulation of serotonin and opioid signaling contributes to pain insensitivity in Nav1.7 knockout mice. Sci Signal. 2017;10: pubmed publisher
    ..7 controls the efficacy and balance of GPCR-mediated pro- and antinociceptive intracellular signaling, such that without Nav1.7, the balance is shifted toward antinociception, resulting in lifelong endogenous analgesia. ..
  28. Dustrude E, Wilson S, Ju W, Xiao Y, Khanna R. CRMP2 protein SUMOylation modulates NaV1.7 channel trafficking. J Biol Chem. 2013;288:24316-31 pubmed publisher
    ..3. Diminution of sodium currents, largely NaV1.7, was recapitulated in sensory neurons expressing CRMP2-K374A. Our study elucidates a novel regulatory mechanism that utilizes CRMP2 SUMOylation to choreograph NaV1.7 trafficking. ..
  29. D ARCANGELO G, Paradiso K, Shepherd D, Brehm P, Halegoua S, Mandel G. Neuronal growth factor regulation of two different sodium channel types through distinct signal transduction pathways. J Cell Biol. 1993;122:915-21 pubmed
    ..These findings suggest that the two sodium channel types act in concert to ensure the generation of action potentials during neuronal differentiation. ..
  30. Yanpallewar S, Wang T, Koh D, Quarta E, Fulgenzi G, Tessarollo L. Nedd4-2 haploinsufficiency causes hyperactivity and increased sensitivity to inflammatory stimuli. Sci Rep. 2016;6:32957 pubmed publisher
    ..These data also suggest that in human, SNPs affecting NEDD4L levels may be involved in the development of neuropsychological deficits and peripheral neuropathies and may help unveil the genetic basis of comorbidities. ..