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Nav1.2

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Target not currently curated in GtoImmuPdb

Target id: 579

Nomenclature: Nav1.2

Family: Voltage-gated sodium channels (NaV)

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 4 2005 2q24.3 SCN2A sodium voltage-gated channel alpha subunit 2 2,49
Mouse 24 4 2006 2 C1.3 Scn2a sodium channel, voltage-gated, type II, alpha
Rat 24 4 2005 3q21 Scn2a sodium voltage-gated channel alpha subunit 2 3,37
Previous and Unofficial Names Click here for help
RII | Brain-II | Brain type-II | Rat-II | NaCh2 | Scn2a1 | sodium channel, voltage-gated, type II, alpha subunit | sodium channel, voltage gated, type II alpha subunit | sodium channel, voltage-gated, type II, alpha | sodium channel
Database Links Click here for help
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human Nav1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit, β2
PDB Id:  6J8E
Resolution:  3.0Å
Species:  Human
References:  31
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
β2 13-14,18,47
β1 13-14,17,43
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
β-3 and β-4 subunits also associate with Nav1.2 channels when co-expressed but there are no direct biochemical data on purified sodium channels at present [28,32,51].
Functional Characteristics Click here for help
Activation V0.5 = -24 mV. Fast inactivation (τ = 0.8 ms for peak sodium current).
Ion Selectivity and Conductance Click here for help
Species:  Rat
Rank order:  Na+ [- pS]
References:  42
Species:  Rat
Single channel conductance (pS):  19
References:  42
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  5.9 - 25 HEK 293 cells transiently transfected with Nav1.2. Rat
Inactivation  43.9 - 25
Comments  τact < 0.4ms at Vact; τinact = 0.8ms at 0mV.

Measurements obtained with an intracellular solution containing Cs-aspartate as the primary solute.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -24.0 - 9 CHO cells stably transfected with Nav1.2. Human
Inactivation  -63.0 - 9
Comments  Measurements obtained using cesium fluoride as the major intracellular solute.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -24.3 - 32 HEK 293 cells transiently transfected with Nav1.2. Rat
Inactivation  -63.4 - 32
Comments  Measurements obtained using N-methyl-D-glucamine chloride as the major intracellular solute.
Voltage Dependence Comments
The values given for activation and inactivation parameters are for α-subunits expressed alone in mammalian cells. Co-expression of β-subunits shifts the voltage dependence [32], as does the use of intracellular solutions with other major anions (see table).

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
β-scorpion toxin Css IV Peptide Rn Partial agonist 9.7 pKd - Physiological 8
pKd 9.7 [8]
Holding voltage: Physiological
batrachotoxin Small molecule or natural product Click here for species-specific activity table Rn Agonist 9.1 pKd - Physiological 23
pKd 9.1 (Kd 7.94x10-10 M) [23]
Holding voltage: Physiological
aconitine Small molecule or natural product Rn Partial agonist 5.9 pKd - Physiological 7
pKd 5.9 [7]
Holding voltage: Physiological
veratridine Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 5.2 pKd - Physiological 7
pKd 5.2 (Kd 6.31x10-6 M) [7]
Holding voltage: Physiological
Activator Comments
Veratridine and aconitine have been studied on sodium channels in synaptosomes, which are predominantly Nav1.2. Binding affinity for batrachotoxin is greatly enhanced by the presence of co-activators in binding experiments and by depolarising prepulses in voltage-clamp experiments because of high affinity binding to the open/activated state.
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
GNE-131 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 - - 10
pIC50 8.1 (IC50 7x10-9 M) [10]
Description: IC50s were generated on a PatchXpress automated voltage-clamp platform, with the membrane potential maintained at a voltage yielding full inactivation of the channel.
XPC-5462 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 - - 12
pIC50 8.0 (IC50 1.09x10-8 M) [12]
Description: Concentration responses were measured at holding potentials where channels were maintained at fully inactivated potentials.
relutrigine Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 - - 19
pIC50 6.8 (IC50 1.72x10-7 M) [19]
funapide Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 - - 29
pIC50 6.2 (IC50 6x10-7 M) [29]
Description: Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay
Gating inhibitors Click here for help
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
α-scorpion toxin 2 Peptide Click here for species-specific activity table Rn Slows inactivation 8.7 pKd - Physiological 36
pKd 8.7 Inhibitor of fast activation [36]
Holding voltage: Physiological
huwentoxin IV Peptide Hs Voltage-dependent inhibition 7.8 pKd - - 27
pKd 7.8 [27]
Description: Automated patch clamp (QPatch) of transfected human embryonic kidney cells (HEK293)
Conditions: Holding potential = -65 mV, the potential for half-maximal inactivation of the sodium current
protoxin II Peptide Click here for species-specific activity table Hs Voltage-dependent inhibition 7.4 pKi - -100.0 39
pKi 7.4 [39]
Holding voltage: -100.0 mV
Description: Whole cell voltage clamp of transfected human embryonic kidney cells (HEK293)
Conditions: Holding potential of -100 mV, approximatley the voltage for half-maximal inactivation
α-scorpion toxin 2 Peptide Click here for species-specific activity table Rn Slows inactivation 9.1 pEC50 - -120.0 21
pEC50 9.1 Inhibitor of fast activation [21]
Holding voltage: -120.0 mV
ATX-II Peptide Click here for species-specific activity table Hs Slows inactivation 8.1 pEC50 - -80.0 30
pEC50 8.1 Inhibitor of fast activation [30]
Holding voltage: -80.0 mV
Bc-III Peptide Click here for species-specific activity table Hs Slows inactivation 5.8 pEC50 - -80.0 30
pEC50 5.8 Inhibitor of fast activation [30]
Holding voltage: -80.0 mV
AFT-II Peptide Click here for species-specific activity table Hs Slows inactivation 5.7 pEC50 - -80.0 30
pEC50 5.7 Inhibitor of fast activation [30]
Holding voltage: -80.0 mV
δ-hexatoxin-Mg1a Peptide Rn Slows inactivation 4.5 pEC50 - -90.0 50
pEC50 4.5 Inhibitor of fast activation [50]
Holding voltage: -90.0 mV
View species-specific gating inhibitor tables
Gating Inhibitor Comments
Additional scorpion and sea anemone toxins act as inhibitors of fast inactivation of Nav1.2 channels at higher concentrations [21,30,52].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
μ-conotoxin SmIIIA Peptide Click here for species-specific activity table Rn Pore blocker 8.9 pKd - -80.0 46
pKd 8.9 [46]
Holding voltage: -80.0 mV
GNE-616 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pKd - - 26
pKd 7.9 (Kd 1.2x10-8 M) [26]
Description: Kd determined in a Dynaflow Manual Patch Clamp experiment.
saxitoxin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Pore blocker 8.8 pIC50 - -120.0 6
pIC50 8.8 (IC50 1.7x10-9 M) [6]
Holding voltage: -120.0 mV
tetrodotoxin Small molecule or natural product Click here for species-specific activity table Rn Pore blocker 8.0 pIC50 - -120.0 6
pIC50 8.0 (IC50 1.12x10-8 M) [6]
Holding voltage: -120.0 mV
etidocaine Small molecule or natural product Rn Pore blocker 6.0 pIC50 - -120.0 33
pIC50 6.0 [33]
Holding voltage: -120.0 mV
lidocaine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Pore blocker 5.0 pIC50 - -120.0 34
pIC50 5.0 [34]
Holding voltage: -120.0 mV
phenytoin Small molecule or natural product Approved drug Primary target of this compound Hs Pore blocker 4.9 pIC50 - -62.0 35
pIC50 4.9 [35]
Holding voltage: -62.0 mV
phenytoin Small molecule or natural product Approved drug Rn Pore blocker 4.7 pIC50 - -120.0 34
pIC50 4.7 [34]
Holding voltage: -120.0 mV
lacosamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 4.5 pIC50 - -80.0 1
pIC50 4.5 (IC50 3x10-5 M) [1]
Holding voltage: -80.0 mV
lamotrigine Small molecule or natural product Approved drug Ligand has a PDB structure Rn Pore blocker 4.5 pIC50 - -50.0 24,48
pIC50 4.5 [24,48]
Holding voltage: -50.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
pIC50 values for lidocaine, etidocaine, lamotrigine and phenytoin reflect the Kd values for the resting state of sodium channels are 10 to 100-fold higher than for binding to open and inactivated sodium channels. Many other μ-conotoxins block Nav1.2 channels at higher concentrations [46].
Tissue Distribution Click here for help
Brain, localised at highest density in unmyelinated axons and in developing pre-myelinated axons, and also present in neuronal cell bodies and dendrites.
Species:  Human
Technique:  Immunohistochemistry
References:  45
Spinal cord, localised in unmyelinated axons and motor neurons.
Species:  Rat
Technique:  Immunohistochemistry
References:  5,11,20,44
Brain, localised at highest density in unmyelinated axons and in developing pre-myelinated axons, and also present in neuronal cell bodies and dendrites.
Species:  Rat
Technique:  Immunohistochemistry
References:  44
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0005277 abnormal brainstem morphology PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0001588 abnormal hemoglobin PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0002272 abnormal nervous system electrophysiology PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0009546 absent gastric milk in neonates PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0001575 cyanosis PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0005039 hypoxia PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0002082 postnatal lethality PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0001954 respiratory distress PMID: 10827969 
Scn2a1tm1Mml Scn2a1tm1Mml/Scn2a1tm1Mml
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:98248  MP:0001263 weight loss PMID: 10827969 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Dravet syndrome
Synonyms: Epileptic encephalopathy, early infantile, 6; EIEE6 [OMIM: 607208]
Severe myoclonic epilepsy of infancy; SMEI [OMIM: 607208]
Disease Ontology: DOID:0060171
OMIM: 607208
Orphanet: ORPHA33069
References:  40
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R1312T 3935G>C 40
Disease:  Epileptic encephalopathy, early infantile, 11; EIEE11
Synonyms: Early infantile epileptic encephalopathy [Orphanet: ORPHA1934]
Infantile epileptic encephalopathy [Disease Ontology: DOID:2481]
Disease Ontology: DOID:2481
OMIM: 613721
Orphanet: ORPHA1934
Disease:  Generalized epilepsy with febrile seizures-plus
Disease Ontology: DOID:0060170
Orphanet: ORPHA36387
Disease:  Seizures, benign familial infantile, 3; BFIS3
Synonyms: Benign familial infantile epilepsy [Orphanet: ORPHA306]
Benign familial neonatal-infantile seizures [Orphanet: ORPHA140927]
OMIM: 607745
Orphanet: ORPHA306, ORPHA140927
Role: 
Drugs: 
References:  4,16,49
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R223Q 4
Missense Human V261M 22
Missense Human F430Q 15
Missense Human V892I 4
Missense Human N1001K 41
Missense Human L1003I 4
Missense Human R1319Q 4
Missense Human L1330F 16
Missense Human L1563V 16,49
Missense Human I1596S 15
Disease:  West syndrome
Disease Ontology: DOID:0050562
Orphanet: ORPHA3451
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  Isoform 2
Amino acids:  2005
Nucleotide accession: 
Protein accession: 
References:  2,49
Type:  Splice variant
Species:  Human
Description:  Isoform 1
Amino acids:  2005
Nucleotide accession: 
Protein accession: 
References:  2,49
Biologically Significant Variant Comments
The D209/N209 difference in the sequence for these two variants leads to a shift in the voltage dependence of Nav and altered response to epilepsy mutations [37-38,49].

References

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1. Abdelsayed M, Sokolov S, Ruben PC. (2013) A thermosensitive mutation alters the effects of lacosamide on slow inactivation in neuronal voltage-gated sodium channels, NaV1.2. Front Pharmacol, 4: 121. [PMID:24065921]

2. Ahmed CM, Ware DH, Lee SC, Patten CD, Ferrer-Montiel AV, Schinder AF, McPherson JD, Wagner-McPherson CB, Wasmuth JJ, Evans GA et al.. (1992) Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain. Proc Natl Acad Sci USA, 89 (17): 8220-4. [PMID:1325650]

3. Auld VJ, Goldin AL, Krafte DS, Marshall J, Dunn JM, Catterall WA, Lester HA, Davidson N, Dunn RJ. (1988) A rat brain Na+ channel alpha subunit with novel gating properties. Neuron, 1 (6): 449-61. [PMID:2856097]

4. Berkovic SF, Heron SE, Giordano L, Marini C, Guerrini R, Kaplan RE, Gambardella A, Steinlein OK, Grinton BE, Dean JT, Bordo L, Hodgson BL, Yamamoto T, Mulley JC, Zara F, Scheffer IE. (2004) Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol, 55 (4): 550-7. [PMID:15048894]

5. Boiko T, Rasband MN, Levinson SR, Caldwell JH, Mandel G, Trimmer JS, Matthews G. (2001) Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron, 30 (1): 91-104. [PMID:11343647]

6. Bricelj VM, Connell L, Konoki K, Macquarrie SP, Scheuer T, Catterall WA, Trainer VL. (2005) Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP. Nature, 434 (7034): 763-7. [PMID:15815630]

7. Catterall WA, Morrow CS, Daly JW, Brown GB. (1981) Binding of batrachotoxinin A 20-alpha-benzoate to a receptor site associated with sodium channels in synaptic nerve ending particles. J Biol Chem, 256 (17): 8922-7. [PMID:6114956]

8. Cestèle S, Qu Y, Rogers JC, Rochat H, Scheuer T, Catterall WA. (1998) Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II. Neuron, 21 (4): 919-31. [PMID:9808476]

9. Clare JJ, Tate SN, Nobbs M, Romanos MA. (2000) Voltage-gated sodium channels as therapeutic targets. Drug Discov Today, 5 (11): 506-520. [PMID:11084387]

10. Focken T, Chowdhury S, Zenova A, Grimwood ME, Chabot C, Sheng T, Hemeon I, Decker SM, Wilson M, Bichler P et al.. (2018) Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of N-([1,2,4]Triazolo[4,3- a]pyridin-3-yl)methane-sulfonamides as Potent and Selective hNaV1.7 Inhibitors for the Treatment of Pain. J Med Chem, 61 (11): 4810-4831. [PMID:29737846]

11. Gong B, Rhodes KJ, Bekele-Arcuri Z, Trimmer JS. (1999) Type I and type II Na(+) channel alpha-subunit polypeptides exhibit distinct spatial and temporal patterning, and association with auxiliary subunits in rat brain. J Comp Neurol, 412 (2): 342-52. [PMID:10441760]

12. Goodchild SJ, Shuart NG, Williams AD, Ye W, Parrish RR, Soriano M, Thouta S, Mezeyova J, Waldbrook M, Dean R et al.. (2024) Molecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo. ACS Chem Neurosci, 15 (6): 1169-1184. [PMID:38359277]

13. Hartshorne RP, Catterall WA. (1984) The sodium channel from rat brain. Purification and subunit composition. J Biol Chem, 259 (3): 1667-75. [PMID:6319405]

14. Hartshorne RP, Messner DJ, Coppersmith JC, Catterall WA. (1982) The saxitoxin receptor of the sodium channel from rat brain. Evidence for two nonidentical beta subunits. J Biol Chem, 257 (23): 13888-91. [PMID:6292214]

15. Herlenius E, Heron SE, Grinton BE, Keay D, Scheffer IE, Mulley JC, Berkovic SF. (2007) SCN2A mutations and benign familial neonatal-infantile seizures: the phenotypic spectrum. Epilepsia, 48 (6): 1138-42. [PMID:17386050]

16. Heron SE, Crossland KM, Andermann E, Phillips HA, Hall AJ, Bleasel A, Shevell M, Mercho S, Seni MH, Guiot MC et al.. (2002) Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet, 360 (9336): 851-2. [PMID:12243921]

17. Isom LL, De Jongh KS, Patton DE, Reber BF, Offord J, Charbonneau H, Walsh K, Goldin AL, Catterall WA. (1992) Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science, 256 (5058): 839-42. [PMID:1375395]

18. Isom LL, Ragsdale DS, De Jongh KS, Westenbroek RE, Reber BF, Scheuer T, Catterall WA. (1995) Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell, 83 (3): 433-42. [PMID:8521473]

19. Kahlig KM, Scott L, Hatch RJ, Griffin A, Martinez Botella G, Hughes ZA, Wittmann M. (2022) The novel persistent sodium current inhibitor PRAX-562 has potent anticonvulsant activity with improved protective index relative to standard of care sodium channel blockers. Epilepsia, 63 (3): 697-708. [PMID:35037706]

20. Kaplan MR, Cho MH, Ullian EM, Isom LL, Levinson SR, Barres BA. (2001) Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier. Neuron, 30 (1): 105-19. [PMID:11343648]

21. Leipold E, Lu S, Gordon D, Hansel A, Heinemann SH. (2004) Combinatorial interaction of scorpion toxins Lqh-2, Lqh-3, and LqhalphaIT with sodium channel receptor sites-3. Mol Pharmacol, 65 (3): 685-91. [PMID:14978247]

22. Liao Y, Deprez L, Maljevic S, Pitsch J, Claes L, Hristova D, Jordanova A, Ala-Mello S, Bellan-Koch A, Blazevic D et al.. (2010) Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain, 133 (Pt 5): 1403-14. [PMID:20371507]

23. Linford NJ, Cantrell AR, Qu Y, Scheuer T, Catterall WA. (1998) Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel. Proc Natl Acad Sci USA, 95 (23): 13947-52. [PMID:9811906]

24. Liu G, Yarov-Yarovoy V, Nobbs M, Clare JJ, Scheuer T, Catterall WA. (2003) Differential interactions of lamotrigine and related drugs with transmembrane segment IVS6 of voltage-gated sodium channels. Neuropharmacology, 44 (3): 413-22. [PMID:12604088]

25. Mantegazza M, Yu FH, Catterall WA, Scheuer T. (2001) Role of the C-terminal domain in inactivation of brain and cardiac sodium channels. Proc Natl Acad Sci USA, 98 (26): 15348-53. [PMID:11742069]

26. McKerrall SJ, Nguyen T, Lai KW, Bergeron P, Deng L, DiPasquale A, Chang JH, Chen J, Chernov-Rogan T, Hackos DH et al.. (2019) Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Nav1.7 Inhibitors for the Treatment of Chronic Pain. J Med Chem, 62 (8): 4091-4109. [PMID:30943032]

27. Minassian NA, Gibbs A, Shih AY, Liu Y, Neff RA, Sutton SW, Mirzadegan T, Connor J, Fellows R, Husovsky M et al.. (2013) Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin huwentoxin-IV (μ-TRTX-Hh2a). J Biol Chem, 288 (31): 22707-20. [PMID:23760503]

28. Morgan K, Stevens EB, Shah B, Cox PJ, Dixon AK, Lee K, Pinnock RD, Hughes J, Richardson PJ, Mizuguchi K et al.. (2000) beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. Proc Natl Acad Sci USA, 97 (5): 2308-13. [PMID:10688874]

29. Mulcahy JV, Pajouhesh H, Beckley JT, Delwig A, Du Bois J, Hunter JC. (2019) Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform NaV1.7. J Med Chem, 62 (19): 8695-8710. [PMID:31012583]

30. Oliveira JS, Redaelli E, Zaharenko AJ, Cassulini RR, Konno K, Pimenta DC, Freitas JC, Clare JJ, Wanke E. (2004) Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop. J Biol Chem, 279 (32): 33323-35. [PMID:15169781]

31. Pan X, Li Z, Huang X, Huang G, Gao S, Shen H, Liu L, Lei J, Yan N. (2019) Molecular basis for pore blockade of human Na+ channel Nav1.2 by the μ-conotoxin KIIIA. Science, 363 (6433): 1309-1313. [PMID:30765605]

32. Qu Y, Curtis R, Lawson D, Gilbride K, Ge P, DiStefano PS, Silos-Santiago I, Catterall WA, Scheuer T. (2001) Differential modulation of sodium channel gating and persistent sodium currents by the beta1, beta2, and beta3 subunits. Mol Cell Neurosci, 18 (5): 570-80. [PMID:11922146]

33. Ragsdale DS, McPhee JC, Scheuer T, Catterall WA. (1994) Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science, 265 (5179): 1724-8. [PMID:8085162]

34. Ragsdale DS, McPhee JC, Scheuer T, Catterall WA. (1996) Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels. Proc Natl Acad Sci USA, 93 (17): 9270-5. [PMID:8799190]

35. Ragsdale DS, Scheuer T, Catterall WA. (1991) Frequency and voltage-dependent inhibition of type IIA Na+ channels, expressed in a mammalian cell line, by local anesthetic, antiarrhythmic, and anticonvulsant drugs. Mol Pharmacol, 40 (5): 756-65. [PMID:1658608]

36. Rogers JC, Qu Y, Tanada TN, Scheuer T, Catterall WA. (1996) Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit. J Biol Chem, 271 (27): 15950-62. [PMID:8663157]

37. Sarao R, Gupta SK, Auld VJ, Dunn RJ. (1991) Developmentally regulated alternative RNA splicing of rat brain sodium channel mRNAs. Nucleic Acids Res, 19 (20): 5673-9. [PMID:1658739]

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