Affinage

SCN11A

Sodium channel protein type 11 subunit alpha · UniProt Q9UI33

Length
1791 aa
Mass
204.9 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCN11A encodes Nav1.9, a tetrodotoxin-resistant voltage-gated sodium channel preferentially expressed in small-diameter nociceptive neurons of dorsal root ganglia, trigeminal ganglia, and the enteric nervous system, where it generates a persistent, low-threshold sodium current that sets resting membrane potential and amplifies subthreshold depolarizations to control nociceptor excitability (PMID:9671787, PMID:11972962, PMID:12684457). Nav1.9 activity is potentiated by Gi/o-coupled G-protein signaling—triggered by inflammatory mediators such as PGE2 and by coincident application of multiple mediators—through increases in single-channel open probability and mean open time rather than unitary conductance (PMID:15374752, PMID:23359282, PMID:18270172). The channel is targeted to the neuronal surface by the cell adhesion molecule contactin and its C-terminus binds FHF1B, while its slow open-state inactivation depends on the conserved IFM motif in the DIII–DIV linker (PMID:11581273, PMID:11376006, PMID:25916202). Gain-of-function SCN11A mutations cause a spectrum of heritable pain disorders—from familial episodic pain to congenital insensitivity to pain—explained by a U-shaped relationship between resting potential depolarization and action potential generation, whereby moderate depolarization produces hyperexcitability (pain) and excessive depolarization causes depolarization block (pain insensitivity) (PMID:24207120, PMID:24036948, PMID:28530638).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    The identification of Nav1.9 as a distinct TTX-resistant sodium channel subunit preferentially expressed in small sensory neurons established SCN11A as a nociceptor-specific ion channel gene, opening the question of what current it carries and what pain modalities it serves.

    Evidence cDNA cloning, sequence alignment, Northern blot, in situ hybridization, and axotomy model in rat DRG

    PMID:9671787

    Open questions at the time
    • No functional current had yet been recorded from cloned Nav1.9
    • Heterologous expression system not yet established
  2. 2002 High

    Biophysical characterization revealed that Nav1.9 carries a persistent TTX-resistant current with uniquely broad overlap between activation and inactivation, establishing its role as a subthreshold amplifier that modulates resting membrane potential rather than driving fast action potentials.

    Evidence Whole-cell patch-clamp electrophysiology in native DRG neurons, synthesis of biophysical data across labs

    PMID:11972962 PMID:15121184

    Open questions at the time
    • Contribution to specific pain modalities in vivo not yet demonstrated
    • Molecular basis of the unusually slow inactivation unknown
  3. 2001 High

    Discovery that contactin promotes Nav1.9 surface expression and that FHF1B selectively binds the Nav1.9 C-terminus identified the first protein partners governing channel trafficking and potentially gating.

    Evidence Co-immunoprecipitation from DRG tissue and heterologous cells, yeast two-hybrid screen with in vitro pull-down confirmation

    PMID:11376006 PMID:11581273

    Open questions at the time
    • Functional consequence of FHF1B binding on channel gating not determined
    • Whether contactin loss phenocopies Nav1.9 loss in vivo was untested
  4. 2004 High

    Knockout of SCN11A proved Nav1.9 is required for inflammatory thermal hypersensitivity and spontaneous pain but dispensable for basal nociception and nerve injury pain, delineating its selective role in inflammatory sensitization.

    Evidence SCN11A-null mice, patch-clamp, and behavioral nociception assays (carrageenan, formalin models)

    PMID:15964986

    Open questions at the time
    • Role in chronic arthritis and cold pain not yet tested
    • Mechanism by which inflammation selectively engages Nav1.9 unclear
  5. 2004 High

    PGE2 was shown to upregulate Nav1.9 current via Gi/o-coupled G-proteins, and multiple inflammatory mediators were later found to potentiate Nav1.9 only when applied coincidentally, establishing Nav1.9 as a coincidence detector for inflammatory signals.

    Evidence Patch-clamp in Nav1.8-null DRG neurons with pertussis/cholera toxin pharmacology; KO neurons with inflammatory mediator cocktail and GTPγS dialysis

    PMID:15374752 PMID:18096591 PMID:18270172

    Open questions at the time
    • Identity of the specific Gi/o subunit(s) and downstream effectors coupling to the channel unknown
    • Whether coincidence detection operates in vivo during inflammation not shown
  6. 2013 High

    Single-channel analysis of G-protein–potentiated human Nav1.9 revealed the mechanism is an increase in open probability and mean open time without altered unitary conductance, providing a biophysical explanation for inflammatory sensitization.

    Evidence Single-channel and whole-cell patch-clamp in ND7/23 cells stably expressing human Nav1.9 with intracellular GTPγS

    PMID:23359282

    Open questions at the time
    • Whether G-protein acts directly on the channel or via an intermediary not resolved
    • Structural basis for G-protein modulation unknown
  7. 2013 High

    Human genetic discoveries linked SCN11A gain-of-function mutations both to familial episodic pain and, paradoxically, to congenital pain insensitivity, posing the question of how activating mutations can produce opposite phenotypes.

    Evidence Exome sequencing, genome-wide linkage, electrophysiology of mutant channels in DRG neurons, knock-in mouse model

    PMID:24036948 PMID:24207120

    Open questions at the time
    • Mechanistic explanation for the divergent phenotypes not yet provided
    • Incomplete genotype–phenotype correlations across mutations
  8. 2015 High

    Chimeric channel engineering showed the C-terminus limits heterologous expression and identified the IFM motif in the DIII–DIV linker as mediating slow open-state inactivation, while the S360Y mutation restored TTX sensitivity, resolving long-standing technical barriers and structural determinants of Nav1.9 gating.

    Evidence Nav1.9/Nav1.4 chimeras expressed in HEK 293T cells and Xenopus oocytes, patch-clamp, mutagenesis

    PMID:25916202

    Open questions at the time
    • No full-length Nav1.9 cryo-EM or crystal structure available
    • Structural basis for TTX resistance beyond S360 not fully mapped
  9. 2015 High

    Nav1.9 was established as a subthreshold amplifier in cold-sensitive nociceptors, with Nav1.9-null mice showing elevated cold pain thresholds and protection from oxaliplatin-induced cold allodynia, extending its role beyond inflammatory heat pain.

    Evidence Nav1.9 knockout mice, antisense knockdown rats, electrophysiology, behavioral cold pain assays

    PMID:25959819 PMID:26645915

    Open questions at the time
    • Molecular mechanism linking cold transducers to Nav1.9 activation not identified
    • Relative contribution of Nav1.9 versus other Nav channels to cold allodynia not quantified
  10. 2017 High

    The paradox of gain-of-function mutations causing either pain or pain insensitivity was resolved by demonstrating a U-shaped relationship between resting potential depolarization and AP threshold: moderate Nav1.9 gain-of-function depolarizes neurons into hyperexcitability while extreme gain-of-function causes depolarization block.

    Evidence Patch-clamp in transfected heterologous cells and rat DRG neurons comparing pain-causing versus pain-insensitivity mutations

    PMID:28530638

    Open questions at the time
    • Quantitative thresholds defining the transition from hyperexcitability to block not established for all mutations
    • Whether compensatory mechanisms modulate the phenotype in vivo unknown
  11. 2018 High

    Nav1.9 was shown to contribute to itch signaling, with pruritogens modulating Nav1.9-dependent gating in DRG neurons and Nav1.9 gain-of-function mice exhibiting spontaneous scratching, expanding the channel's role beyond pain.

    Evidence Nav1.9-null, Nav1.9 gain-of-function (L799P), and fluorescent Nav1.9 knock-in mice with patch-clamp and behavioral pruritogen assays

    PMID:30395542

    Open questions at the time
    • Pruritogen receptor–Nav1.9 signaling pathway not delineated
    • Relative contribution to chronic itch conditions untested
  12. 2019 High

    Nav1.9 was identified as the effector channel mediating NO-dependent triptan-induced medication overuse headache, linking its activation to CGRP release from meningeal nociceptors and mast cell degranulation in a feed-forward loop.

    Evidence SCN11A-null mice, electrophysiology in dural afferent neurons, CGRP release and mast cell assays, behavioral MOH model

    PMID:31534133

    Open questions at the time
    • Direct binding site or mechanism of NO-mediated Nav1.9 activation not identified
    • Translational relevance to human MOH not clinically validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for G-protein modulation and NO activation of Nav1.9, the identity of the specific Gβγ or Gα subunit that directly acts on the channel, and whether Nav1.9-selective pharmacology can be achieved for therapeutic targeting of pain and itch.
  • No high-resolution structure of Nav1.9 available
  • No Nav1.9-selective small-molecule inhibitor reported
  • Direct G-protein binding site on the channel not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4
Partners
CNTN1FHF1BSCN1BSCN2BTNC

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NaN (Nav1.9/SCN11A) was identified as a novel voltage-gated Na+ channel alpha-subunit predicted to be tetrodotoxin-resistant, preferentially expressed in small sensory neurons of dorsal root ganglia and trigeminal ganglia; NaN mRNA levels are significantly reduced 7 days post-axotomy, consistent with reduction in TTX-R Na+ currents. cDNA cloning, sequence alignment, Northern blot/in situ hybridization, axotomy model Proceedings of the National Academy of Sciences of the United States of America High 9671787
2002 Nav1.9 produces a persistent, tetrodotoxin-resistant Na+ current with wide overlap between activation and steady-state inactivation, modulating resting potential and amplifying small depolarizations in primary nociceptive neurons. Whole-cell patch-clamp electrophysiology in DRG neurons, review/synthesis of biophysical data Trends in neurosciences High 11972962
2001 Fibroblast growth factor homologous factor 1B (FHF1B) directly interacts with the C-terminal region of Nav1.9a (NaN); FHF1B binds selectively to the C-terminus of Nav1.9a but not to the C-termini of Nav1.7 or Nav1.8, identified via yeast two-hybrid screen and confirmed by in vitro binding and co-expression in mammalian cells. Yeast two-hybrid screen, in vitro pull-down, co-expression in mammalian cell lines The Journal of biological chemistry High 11376006
2001 Cell adhesion molecule contactin directly binds to Nav1.9/NaN and recruits tenascin to the protein complex; contactin co-immunoprecipitates with Nav1.9 from DRG and transfected CHO cells, co-localizes along nonmyelinated C-fibers and nerve endings, and enhances surface expression of Nav1.9. Co-immunoprecipitation from DRG tissue and CHO cells, co-transfection surface expression assay, immunohistochemistry The Journal of biological chemistry High 11581273
2004 Nav1.9 underlies the persistent TTX-resistant current in small-diameter DRG neurons; Nav1.9 contributes to persistent thermal hypersensitivity and spontaneous pain behavior after peripheral inflammation but not to basal mechanical/thermal responsiveness or nerve injury-induced mechanical hypersensitivity. SCN11A gene knockout mice, patch-clamp electrophysiology, behavioral nociception assays Proceedings of the National Academy of Sciences of the United States of America High 15964986
2004 PGE2 increases Nav1.9 current approximately two-fold in DRG neurons via a G-protein-dependent mechanism involving Gi/o subunits (blocked by pertussis toxin but not cholera toxin), shifting steady-state activation hyperpolarized by 6-8 mV and availability by 12 mV. Whole-cell patch-clamp in Nav1.8-null and wild-type mouse DRG neurons, pertussis toxin and cholera toxin pharmacology Brain research High 15374752
2003 Nav1.9 generates a TTX-resistant persistent Na+ current selectively in myenteric sensory (IPAN) neurons of the enteric nervous system but not in interneurons or motor neurons, confirmed by RT-PCR, single-cell profiling, immunostaining, and patch-clamp. Whole-cell patch-clamp, RT-PCR, single-cell profiling, immunostaining in guinea pig and rat myenteric neurons The Journal of neuroscience High 12684457
2004 Single-channel and whole-cell recordings establish that Nav1.9 channels have long openings and high open probability; intracellular fluoride promotes entry into a preopen closed state, biasing channels towards opening and enhancing nociceptor spiking. Single-channel and whole-cell patch-clamp recordings in cultured rat DRG and myenteric neurons Molecular and cellular neurosciences High 15121184
2007 GTP (via GTPγS, a G-protein activator) upregulates the persistent TTX-resistant Na+ current and causes a negative shift in voltage threshold in small DRG neurons; this effect is absent in Nav1.9-null neurons and restored by heterologous expression of human Nav1.9, demonstrating Nav1.9 is the molecular target of G-protein pathway modulation. Nav1.9 knockout mice, intracellular GTPγS dialysis, patch-clamp, rescue by heterologous hNav1.9 expression The Journal of physiology High 18096591
2008 Nav1.9 subunits carry the TTX-resistant persistent Na+ current (NaN) in small DRG neurons; loss of Nav1.9 eliminates subthreshold regenerative depolarizations, plateau potentials, active hyperpolarizing responses, oscillatory bursting, and bistable membrane behaviors. When applied conjointly (but not individually), a soup of inflammatory mediators (bradykinin, ATP, histamine, PGE2, norepinephrine) potentiates Nav1.9 channel activity through a coincident detection mechanism. Nav1.9 gene targeting (knockout), whole-cell patch-clamp with CsCl and KCl pipette solutions, computer modeling, pharmacological application of inflammatory mediators The Journal of general physiology High 18270172
2013 G-protein activation (GTPγS) potentiates human Nav1.9 by increasing single-channel open probability and mean open time (not single-channel amplitude), causing larger peak and persistent currents; G-protein signaling also slows inactivation and causes a depolarizing shift in voltage-dependence of inactivation without changing activation voltage-dependence. Whole-cell and single-channel patch-clamp in ND7/23 cells stably expressing human Nav1.9, intracellular GTPγS The Journal of general physiology High 23359282
2013 A specific de novo gain-of-function missense mutation in SCN11A causes excessive Nav1.9 activity at resting voltages, sustained depolarization of nociceptors, impaired action potential generation, and aberrant synaptic transmission, resulting in congenital inability to experience pain in humans and recapitulated in knock-in mice. Exome sequencing, heterozygous knock-in mouse model, patch-clamp electrophysiology in DRG neurons Nature genetics High 24036948
2013 Two gain-of-function missense mutations in SCN11A (p.Arg225Cys and p.Ala808Gly) enhance Nav1.9 electrical activity and induce hyperexcitability of DRG neurons, causing autosomal-dominant familial episodic pain. Genome-wide linkage scan, exome sequencing, expression of mutant Nav1.9 in mouse DRG neurons, electrophysiology American journal of human genetics High 24207120
2015 Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons; Nav1.9 activity is upregulated in neurons responding to cooling, amplifying subthreshold depolarizations from cold transducers; Nav1.9-null mice and knockdown rats show increased cold pain thresholds, and Nav1.9 loss alleviates oxaliplatin-induced cold allodynia. Nav1.9 knockout mice, antisense knockdown rats, electrophysiology, behavioral cold pain assays Cell reports High 25959819
2015 A gain-of-function SCN11A mutation (p.V1184A) shifts the voltage dependence of Nav1.9 channel opening to hyperpolarized potentials, reducing resting membrane potential of mouse primary sensory neurons and causing cold-resistant hyperexcitability of nociceptors, causing cold-aggravated peripheral pain in humans. Exome sequencing, patch-clamp electrophysiology in mouse DRG neurons transfected with mutant Nav1.9 Nature communications High 26645915
2017 Nav1.9 mutations associated with pain insensitivity (L1302F, L811P) cause large hyperpolarizing shifts in voltage-dependence of activation and evoke large resting membrane potential depolarizations in DRG neurons, impairing action potential generation (cellular loss of function). A U-shaped relationship between resting potential and action potential threshold explains why small depolarizations cause hyperexcitability (pain) while large depolarizations cause hypoexcitability (pain insensitivity). Patch-clamp in transfected heterologous cells and rat DRG neurons, current-clamp recordings The Journal of clinical investigation High 28530638
2016 Stable heterologous expression of human, mouse, and rat Nav1.9 in HEK-293 cells was achieved by co-expression with β1/β2 subunits; a unique lysine residue (K799) in Domain 2 S6 of Nav1.9 influences interaction of inhibitors (tetracaine, TC-N 1752) with the pore, as shown by K799N mutation. Stable HEK-293 cell expression, patch-clamp, site-directed mutagenesis (K799N), pharmacological profiling PloS one High 27556810
2015 Poor heterologous expression of Nav1.9 is caused by its C-terminal structure; a chimera of Nav1.9 with the C-terminus of Nav1.4 enables functional expression in HEK 293T cells and Xenopus oocytes. The slow open-state inactivation of Nav1.9 is mediated by the IFM inactivation motif in the DIII-DIV linker, and mutation S360Y renders Nav1.9 sensitive to tetrodotoxin and saxitoxin. Chimeric channel construction, patch-clamp, two-electrode voltage-clamp in Xenopus oocytes, mutagenesis (S360Y) Pflugers Archiv : European journal of physiology High 25916202
2019 Abnormal activation of Nav1.9 channels by nitric oxide (NO) causes triptan-induced medication overuse headache (MOH); deletion of Scn11a abrogates NO-mediated symptoms; Nav1.9 activation triggers CGRP secretion causing artery dilatation and mast cell degranulation, which in turn potentiates Nav1.9 in meningeal nociceptors. PKA is downregulated in trigeminal neurons from MOH mice, relieving inhibitory action on NO-Nav1.9 coupling. Scn11a knockout mice, electrophysiology in dural afferent neurons, signaling network analysis, behavioral assays Nature communications High 31534133
2018 Nav1.9 is expressed in a subset of nonmyelinated, nonpeptidergic small-diameter DRG neurons; pruritogens alter action potential parameters and Nav channel gating in wild-type but not Nav1.9-null DRG neurons; Nav1.9-null mice show reduced acute scratching to pruritogens while Nav1.9 gain-of-function mice (L799P) display increased spontaneous scratching, establishing Nav1.9 as a contributor to itch signaling. Fluorescent-tagged Nav1.9 knock-in mouse, Nav1.9 knockout and Nav1.9-L799P knock-in mice, patch-clamp, behavioral pruritogen assays The Journal of clinical investigation High 30395542
2011 Nav1.9 contributes to heat and mechanical pain hypersensitivity in subacute (carrageenan) and chronic (CFA monoarthritis) inflammatory pain models; Nav1.9 immunoreactivity increases in ipsilateral DRGs 24 hours after carrageenan, correlating with increased axonal transport, without change in current density at the soma. Nav1.9-null mice, antisense knockdown rats, behavioral tests (von Frey, dynamic weight bearing, Hargreaves), immunohistochemistry, patch-clamp PloS one High 21857998
2019 A novel Nav1.9 gain-of-function mutation (N816K) increases current density, hyperpolarizes voltage-dependence of activation by 10 mV, enlarges window current, depolarizes resting membrane potential of small DRG neurons by 7 mV, and renders DRG neurons hyperexcitable in a child with episodic pain. Voltage-clamp and current-clamp in transfected rat DRG neurons, Sanger sequencing Frontiers in neuroscience Medium 31551682
2017 Nav1.9-null C-fibers show elevated electrical threshold (by 55%), reduced prevalence of mechano-heat sensitive C-fibers, elevated heat thresholds, lower activity-induced slowing of conduction velocity on noxious heat, and reduced heat-induced CGRP release from skin, demonstrating Nav1.9 contributes to acute thermal and mechanical nociception by increasing excitability and amplifying receptor potentials. Single-fiber electrophysiology from isolated skin, compound action potential recordings, CGRP release assay, Hargreaves test, Nav1.9 knockout mice Pain High 27780178
2013 Amitriptyline inhibits Nav1.9 currents in a concentration-dependent and state-selective manner (IC50 ~15 µM in TG neurons), shifting steady-state inactivation hyperpolarized without affecting activation, and without use-dependent block. Whole-cell patch-clamp in acutely isolated rat trigeminal ganglion neurons Molecular pain Medium 24228717
2019 Protein kinase C-α (PKCα) upregulates Nav1.9 expression in nociceptive DRG neurons in a CFA-induced arthritis pain model; PKC activator (PMA) increases Nav1.9 expression in cultured DRG neurons and in vivo, while PKC inhibitor (GF-109203X) decreases Nav1.9 expression and attenuates hyperalgesia. In vitro and in vivo PKC modulator treatment, qPCR, Western blot, immunofluorescence, behavioral tests Journal of cellular biochemistry Medium 31385361

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy. Proceedings of the National Academy of Sciences of the United States of America 419 9671787
1999 A comparison of the potential role of the tetrodotoxin-insensitive sodium channels, PN3/SNS and NaN/SNS2, in rat models of chronic pain. Proceedings of the National Academy of Sciences of the United States of America 259 10393873
2013 A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nature genetics 240 24036948
2005 Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior. Proceedings of the National Academy of Sciences of the United States of America 222 15964986
2002 NaN/Nav1.9: a sodium channel with unique properties. Trends in neurosciences 205 11972962
1985 Identification of an inducible catabolic system for sialic acids (nan) in Escherichia coli. Journal of bacteriology 192 3902799
2000 Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states. Pain 174 10692601
2013 Gain-of-function mutations in SCN11A cause familial episodic pain. American journal of human genetics 155 24207120
1990 Mixed agonist/antagonist properties of NAN-190 at 5-HT1A receptors: behavioural and in vivo brain microdialysis studies. Life sciences 143 2329921
2004 PGE2 increases the tetrodotoxin-resistant Nav1.9 sodium current in mouse DRG neurons via G-proteins. Brain research 139 15374752
2008 Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. The Journal of general physiology 136 18270172
2007 Pharmacological dissection and distribution of NaN/Nav1.9, T-type Ca2+ currents, and mechanically activated cation currents in different populations of DRG neurons. The Journal of general physiology 125 17190903
2001 Fibroblast growth factor homologous factor 1B binds to the C terminus of the tetrodotoxin-resistant sodium channel rNav1.9a (NaN). The Journal of biological chemistry 115 11376006
2003 Selective expression of a persistent tetrodotoxin-resistant Na+ current and NaV1.9 subunit in myenteric sensory neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 114 12684457
2004 Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons. Molecular and cellular neurosciences 103 15121184
2007 GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9. The Journal of physiology 95 18096591
1992 The putative 5-HT1A receptor antagonists NAN-190 and BMY 7378 are partial agonists in the rat dorsal raphe nucleus in vitro. European journal of pharmacology 94 1535319
2011 Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation. PloS one 87 21857998
2017 An Innovative Freeze-Dried Reduced Graphene Oxide Supported SnS2 Cathode Active Material for Aluminum-Ion Batteries. Advanced materials (Deerfield Beach, Fla.) 86 28370537
1990 NAN-190: agonist and antagonist interactions with brain 5-HT1A receptors. Brain research 83 2282513
2017 Sodium channel NaV1.9 mutations associated with insensitivity to pain dampen neuronal excitability. The Journal of clinical investigation 70 28530638
2015 Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant. Nature communications 70 26645915
2001 Direct interaction with contactin targets voltage-gated sodium channel Na(v)1.9/NaN to the cell membrane. The Journal of biological chemistry 68 11581273
2021 Identifying infectiousness of SARS-CoV-2 by ultra-sensitive SnS2 SERS biosensors with capillary effect. Matter 67 34957388
2015 The Nav1.9 channel is a key determinant of cold pain sensation and cold allodynia. Cell reports 65 25959819
2010 Severe anemia in the Nan mutant mouse caused by sequence-selective disruption of erythroid Kruppel-like factor. Proceedings of the National Academy of Sciences of the United States of America 65 20696915
2019 Synthesis and Application of CeO2/SnS2 Heterostructures as a Highly Efficient Coreaction Accelerator in the Luminol-Dissolved O2 System for Ultrasensitive Biomarkers Immunoassay. Analytical chemistry 62 31595739
1997 Influence of 5-HT1A receptor antagonism on plus-maze behaviour in mice. II. WAY 100635, SDZ 216-525 and NAN-190. Pharmacology, biochemistry, and behavior 59 9300624
1991 Effect of the putative 5-HT1A receptor antagonist NAN-190 on rat brain serotonergic transmission. European journal of pharmacology 59 1666563
1990 The behavioural, but not the hypothermic or corticosterone, response to 8-hydroxy-2-(DI-n-propylamino)-tetralin, is antagonized by NAN-190 in the rat. Neuropharmacology 54 2143565
1999 Coding sequence, genomic organization, and conserved chromosomal localization of the mouse gene Scn11a encoding the sodium channel NaN. Genomics 51 10444332
2013 Mechanism of sodium channel NaV1.9 potentiation by G-protein signaling. The Journal of general physiology 49 23359282
2016 Changes in the expression of voltage-gated sodium channels Nav1.3, Nav1.7, Nav1.8, and Nav1.9 in rat trigeminal ganglia following chronic constriction injury. Neuroreport 46 27327156
2018 A disease mutation reveals a role for NaV1.9 in acute itch. The Journal of clinical investigation 45 30395542
2016 Biophysical and Pharmacological Characterization of Nav1.9 Voltage Dependent Sodium Channels Stably Expressed in HEK-293 Cells. PloS one 45 27556810
2015 Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9. Bone 45 26746779
2000 SNS/PN3 and SNS2/NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves. FEBS letters 45 10675548
2020 Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels. Pflugers Archiv : European journal of physiology 44 32601768
2013 Epidemiology and clinical features of rotavirus and norovirus infection among children in Ji'nan, China. Virology journal 43 24099150
2019 Quench-type electrochemiluminescence immunosensor for detection of amyloid β-protein based on resonance energy transfer from luminol@SnS2-Pd to Cu doped WO3 nanoparticles. Biosensors & bioelectronics 41 30928738
2016 Infantile Pain Episodes Associated with Novel Nav1.9 Mutations in Familial Episodic Pain Syndrome in Japanese Families. PloS one 41 27224030
2017 Large-scale seaweed cultivation diverges water and sediment microbial communities in the coast of Nan'ao Island, South China Sea. The Science of the total environment 38 28437776
2010 Mutation in erythroid specific transcription factor KLF1 causes Hereditary Spherocytosis in the Nan hemolytic anemia mouse model. Genomics 38 20691777
2002 NAN fusions: a synthetic sialidase reporter gene as a sensitive and versatile partner for GUS. The Plant journal : for cell and molecular biology 38 12410816
2018 Ultrasensitive photoelectrochemical immunosensor for the detection of amyloid β-protein based on SnO2/SnS2/Ag2S nanocomposites. Biosensors & bioelectronics 36 30142477
2012 Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain. Neuroscience letters 35 22342308
2000 Identification of a novel human voltage-gated sodium channel alpha subunit gene, SCN12A. Biochemical and biophysical research communications 35 10623608
2017 Flexible Paper-like Free-Standing Electrodes by Anchoring Ultrafine SnS2 Nanocrystals on Graphene Nanoribbons for High-Performance Sodium Ion Batteries. ACS applied materials & interfaces 34 28429929
2015 The role of Nav1.9 channel in the development of neuropathic orofacial pain associated with trigeminal neuralgia. Molecular pain 34 26607325
2020 Ultrasensitive Photoelectrochemical Assay for DNA Detection Based on a Novel SnS2/Co3O4 Sensitized Structure. Analytical chemistry 33 33047953
2017 Gain-of-function mutation p.Arg225Cys in SCN11A causes familial episodic pain and contributes to essential tremor. Journal of human genetics 33 28298626
2009 5-HT antagonists NAN-190 and SB 269970 block alpha2-adrenoceptors in the guinea pig. Neuroreport 33 19190523
2007 Expression of Nav1.9 channels in human dental pulp and trigeminal ganglion. Journal of endodontics 33 17889684
2013 Correlation of Nav1.8 and Nav1.9 sodium channel expression with neuropathic pain in human subjects with lingual nerve neuromas. Molecular pain 32 24144460
2019 Maladaptive activation of Nav1.9 channels by nitric oxide causes triptan-induced medication overuse headache. Nature communications 30 31534133
2018 SnS2 Nanosheets Coating on Nanohollow Cubic CoS2 /C for Ultralong Life and High Rate Capability Half/Full Sodium-Ion Batteries. Small (Weinheim an der Bergstrasse, Germany) 30 30152599
2017 Rapidly Synthesized, Few-Layered Pseudocapacitive SnS2 Anode for High-Power Sodium Ion Batteries. ACS applied materials & interfaces 29 29076723
2015 Heterologous expression of NaV1.9 chimeras in various cell systems. Pflugers Archiv : European journal of physiology 29 25916202
2019 SnS2@C Hollow Nanospheres with Robust Structural Stability as High-Performance Anodes for Sodium Ion Batteries. Nano-micro letters 28 34137992
1992 Discriminative stimulus effects of 8-OH-DPAT in pigeons: antagonism studies with the putative 5-HT1A receptor antagonists BMY 7378 and NAN-190. European journal of pharmacology 28 1425937
2022 Apatinib plus vinorelbine versus vinorelbine for metastatic triple-negative breast cancer who failed first/second-line treatment: the NAN trial. NPJ breast cancer 27 36127351
2008 Increased nerve fiber expression of sensory sodium channels Nav1.7, Nav1.8, And Nav1.9 in rhinitis. The Laryngoscope 25 18197135
2008 Primary erythermalgia as a sodium channelopathy: screening for SCN9A mutations: exclusion of a causal role of SCN10A and SCN11A. Archives of dermatology 25 18347287
2019 Characterization of 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN) as a Novel Opioid Receptor Modulator for Opioid Use Disorder Treatment. ACS chemical neuroscience 24 30758946
2019 A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain. Frontiers in neuroscience 24 31551682
1991 Is NAN-190 an effective antagonist of the hypothermia and hyperglycemia induced by the 5-HT1A receptor agonist, 8-OH-DPAT? European journal of pharmacology 24 1828770
2018 Improved Electrochemical Performance Based on Nanostructured SnS2@CoS2-rGO Composite Anode for Sodium-Ion Batteries. Nano-micro letters 23 30393695
1996 Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram. Behavioural brain research 23 8800653
1993 Withdrawal from continuous or intermittent cocaine: effects of NAN-190 on cocaine-induced locomotion. Pharmacology, biochemistry, and behavior 23 8446658
2013 Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons. Molecular pain 22 24228717
2023 Effects of konjac glucan-nan/low-acyl gellan edible coatings loaded thymol-β-cyclodextrin microcapsules on postharvest blueberry. Food chemistry 21 37549621
2019 A Plasma-Triggered O-S Bond and P-N Junction Near the Surface of a SnS2 Nanosheet Array to Enable Efficient Solar Water Oxidation. Angewandte Chemie (International ed. in English) 21 31507028
2017 Neomorphic effects of the neonatal anemia (Nan-Eklf) mutation contribute to deficits throughout development. Development (Cambridge, England) 21 28143845
2023 Fast Energy Storage of SnS2 Anode Nanoconfined in Hollow Porous Carbon Nanofibers for Lithium-Ion Batteries. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 38041500
2021 Ag functionalized SnS2 with enhanced photothermal activity for safe and efficient wound disinfection. Biomaterials science 20 34032227
2008 Enhancement of photic shifts with the 5-HT1A mixed agonist/antagonist NAN-190: intra-suprachiasmatic nucleus pathway. Neuroscience 20 18406538
2018 A Simple One-Pot Strategy for Synthesizing Ultrafine SnS2 Nanoparticle/Graphene Composites as Anodes for Lithium/Sodium-Ion Batteries. ChemSusChem 19 29516664
2017 Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice. Pain 19 27780178
2010 Ethanolic cofermentation with glucose and xylose by the recombinant industrial strain Saccharomyces cerevisiae NAN-127 and the effect of furfural on xylitol production. Bioresource technology 19 20456950
1996 The role of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the inhibition of 5-HT release--II NAN-190 and SDZ 216-525. Neuropharmacology 19 8887982
2018 Familial episodic limb pain in kindreds with novel Nav1.9 mutations. PloS one 18 30557356
2016 Development of SnS2/RGO nanosheet composite for cost-effective aqueous hybrid supercapacitors. Nanotechnology 18 27924781
2012 Activation of tetrodotoxin-resistant sodium channel NaV1.9 in rat primary sensory neurons contributes to melittin-induced pain behavior. Neuromolecular medicine 18 23264124
2009 Hematologic characterization and chromosomal localization of the novel dominantly inherited mouse hemolytic anemia, neonatal anemia (Nan). Blood cells, molecules & diseases 18 19409822
2022 Unveiling Targets for Treating Postoperative Pain: The Role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 Pathways in the Mouse Model of Incisional Pain. International journal of molecular sciences 17 36232927
1992 Antagonism studies with BMY-7378 and NAN-190: effects on 8-hydroxy-2-(di-n-propylamino)tetralin-induced increases in punished responding of pigeons. The Journal of pharmacology and experimental therapeutics 17 1531359
2020 Insights into the photocatalysis mechanism of the novel 2D/3D Z-Scheme g-C3N4/SnS2 heterojunction photocatalysts with excellent photocatalytic performances. Journal of hazardous materials 16 33254755
2019 Protein kinase C-α upregulates sodium channel Nav1.9 in nociceptive dorsal root ganglion neurons in an inflammatory arthritis pain model of rat. Journal of cellular biochemistry 16 31385361
2018 SCN11A Arg225Cys mutation causes nociceptive pain without detectable peripheral nerve pathology. Neurology. Genetics 16 30046661
2016 Decreased Nav1.9 channel expression in Hirschsprung's disease. Journal of pediatric surgery 16 27297039
2014 Nav1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus. Experimental neurology 16 24424281
2019 A dual mode photoelectrochemical sensor for nitrobenzene and L-cysteine based on 3D flower-like Cu2SnS3@SnS2 double interfacial heterojunction photoelectrode. Journal of hazardous materials 15 31446355
2022 Navigated Delivery of Peptide to the Nanopore Using In-Plane Heterostructures of MoS2 and SnS2 for Protein Sequencing. The journal of physical chemistry letters 14 35467868
2021 Transcriptome-Wide m6A Analysis Provides Novel Insights Into Testicular Development and Spermatogenesis in Xia-Nan Cattle. Frontiers in cell and developmental biology 14 35004687
2020 Protective effect of astaxanthin against SnS2 nanoflowers induced testes toxicity by suppressing RIPK1-RIPK3-MLKL signaling in mice. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 14 32918989
2018 Mutant KLF1 in Adult Anemic Nan Mice Leads to Profound Transcriptome Changes and Disordered Erythropoiesis. Scientific reports 14 30143664
2018 Physiological and immunological responses to mass mortality in noble scallop Chlamys nobilis cultured in Nan'ao waters of Shantou, China. Fish & shellfish immunology 14 30145199
2017 Self-Assembled Framework Formed During Lithiation of SnS2 Nanoplates Revealed by in Situ Electron Microscopy. Accounts of chemical research 14 28682057
1995 Differential effects of WAY-100135 on the decrease in 5-hydroxytryptamine release induced by buspirone and NAN-190. European journal of pharmacology 14 7601215
2002 Structure of the sodium channel gene SCN11A: evidence for intron-to-exon conversion model and implications for gene evolution. Molecular neurobiology 13 12428758