Na<sub>v</sub>1.2 | Voltage-gated sodium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Nav1.2

Target id: 579

Nomenclature: Nav1.2

Family: Voltage-gated sodium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Nav1.2 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 4 2005 2q22-23 SCN2A sodium voltage-gated channel alpha subunit 2 2,44
Mouse 24 4 2006 2 C1.3 Scn2a sodium channel, voltage-gated, type II, alpha
Rat 24 4 2005 3q24 Scn2a sodium voltage-gated channel alpha subunit 2 3,32
Previous and Unofficial Names
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
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
β2 12-13,17,42
β1 12-13,16,38
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 [25,27,46].
Functional Characteristics
Activation V0.5 = -24 mV. Fast inactivation (τ = 0.8 ms for peak sodium current).
Ion Selectivity and Conductance
Species:  Rat
Rank order:  Na+ [- pS]
References:  37
Species:  Rat
Single channel conductance (pS):  19
References:  37
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  5.9 - 23 HEK 293 cells transiently transfected with Nav1.2. Rat
Inactivation  43.9 - 23
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 - 27 HEK 293 cells transiently transfected with Nav1.2. Rat
Inactivation  -63.4 - 27
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 [27], as does the use of intracellular solutions with other major anions (see table).

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
β-scorpion toxin Css IV Rn Partial agonist 9.7 pKd - Physiological 8
pKd 9.7 [8]
Holding voltage: Physiological
batrachotoxin Rn Agonist 9.1 pKd - Physiological 21
pKd 9.1 (Kd 7.94x10-10 M) [21]
Holding voltage: Physiological
aconitine Rn Partial agonist 5.9 pKd - Physiological 7
pKd 5.9 [7]
Holding voltage: Physiological
veratridine 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 Affinity Units Concentration range (M) Holding voltage (mV) Reference
GNE-131 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.
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
α-scorpion toxin 2 Rn Slows inactivation 8.7 pKd - Physiological 31
pKd 8.7 Inhibitor of fast activation [31]
Holding voltage: Physiological
huwentoxin IV Hs Voltage-dependent inhibition 7.8 pKd - - 24
pKd 7.8 [24]
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 Hs Voltage-dependent inhibition 7.4 pKi - -100.0 34
pKi 7.4 [34]
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 Rn Slows inactivation 9.1 pEC50 - -120.0 19
pEC50 9.1 Inhibitor of fast activation [19]
Holding voltage: -120.0 mV
ATX-II Hs Slows inactivation 8.1 pEC50 - -80.0 26
pEC50 8.1 Inhibitor of fast activation [26]
Holding voltage: -80.0 mV
Bc-III Hs Slows inactivation 5.8 pEC50 - -80.0 26
pEC50 5.8 Inhibitor of fast activation [26]
Holding voltage: -80.0 mV
AFT-II Hs Slows inactivation 5.7 pEC50 - -80.0 26
pEC50 5.7 Inhibitor of fast activation [26]
Holding voltage: -80.0 mV
δ-hexatoxin-Mg1a Rn Slows inactivation 4.5 pEC50 - -90.0 45
pEC50 4.5 Inhibitor of fast activation [45]
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 [19,26,47].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
μ-conotoxin SmIIIA Rn Pore blocker 8.9 pKd - -80.0 41
pKd 8.9 [41]
Holding voltage: -80.0 mV
saxitoxin Rn Pore blocker 8.8 pIC50 - -120.0 6
pIC50 8.8 (IC50 1.7x10-9 M) [6]
Holding voltage: -120.0 mV
tetrodotoxin Rn Pore blocker 8.0 pIC50 - -120.0 6
pIC50 8.0 (IC50 1.12x10-8 M) [6]
Holding voltage: -120.0 mV
etidocaine Rn Pore blocker 6.0 pIC50 - -120.0 28
pIC50 6.0 [28]
Holding voltage: -120.0 mV
lidocaine Rn Pore blocker 5.0 pIC50 - -120.0 29
pIC50 5.0 [29]
Holding voltage: -120.0 mV
phenytoin Hs Pore blocker 4.9 pIC50 - -62.0 30
pIC50 4.9 [30]
Holding voltage: -62.0 mV
phenytoin Rn Pore blocker 4.7 pIC50 - -120.0 29
pIC50 4.7 [29]
Holding voltage: -120.0 mV
lacosamide Rn Antagonist 4.5 pIC50 - -80.0 1
pIC50 4.5 (IC50 3x10-5 M) [1]
Holding voltage: -80.0 mV
lamotrigine Rn Pore blocker 4.5 pIC50 - -50.0 22,43
pIC50 4.5 [22,43]
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 [41].
Tissue Distribution
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:  40
Spinal cord, localised in unmyelinated axons and motor neurons.
Species:  Rat
Technique:  Immunohistochemistry
References:  5,11,18,39
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:  39
Phenotypes, Alleles and Disease Models 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
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:  35
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R1312T 3935G>C 35
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:  4,15,44
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R223Q 4
Missense Human V261M 20
Missense Human F430Q 14
Missense Human V892I 4
Missense Human N1001K 36
Missense Human L1003I 4
Missense Human R1319Q 4
Missense Human L1330F 15
Missense Human L1563V 15,44
Missense Human I1596S 14
Disease:  West syndrome
Disease Ontology: DOID:0050562
Orphanet: ORPHA3451
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  Isoform 2
Amino acids:  2005
Nucleotide accession: 
Protein accession: 
References:  2,44
Type:  Splice variant
Species:  Human
Description:  Isoform 1
Amino acids:  2005
Nucleotide accession: 
Protein accession: 
References:  2,44
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 [32-33,44].

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. (1992) Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain. Proc. Natl. Acad. Sci. U.S.A., 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. Hartshorne RP, Catterall WA. (1984) The sodium channel from rat brain. Purification and subunit composition. J. Biol. Chem., 259 (3): 1667-75. [PMID:6319405]

13. 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]

14. 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]

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

16. 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]

17. 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]

18. 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]

19. 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]

20. 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]

21. 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. U.S.A., 95 (23): 13947-52. [PMID:9811906]

22. 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]

23. 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. U.S.A., 98 (26): 15348-53. [PMID:11742069]

24. 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]

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

26. 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]

27. 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]

28. 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]

29. 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. U.S.A., 93 (17): 9270-5. [PMID:8799190]

30. 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]

31. 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]

32. 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]

33. Schlachter K, Gruber-Sedlmayr U, Stogmann E, Lausecker M, Hotzy C, Balzar J, Schuh E, Baumgartner C, Mueller JC, Illig T et al.. (2009) A splice site variant in the sodium channel gene SCN1A confers risk of febrile seizures. Neurology, 72 (11): 974-8. [PMID:19289736]

34. Schmalhofer WA, Calhoun J, Burrows R, Bailey T, Kohler MG, Weinglass AB, Kaczorowski GJ, Garcia ML, Koltzenburg M, Priest BT. (2008) ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. Mol. Pharmacol., 74 (5): 1476-84. [PMID:18728100]

35. Shi X, Yasumoto S, Nakagawa E, Fukasawa T, Uchiya S, Hirose S. (2009) Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome. Brain Dev., 31 (10): 758-62. [PMID:19783390]

36. Striano P, Bordo L, Lispi ML, Specchio N, Minetti C, Vigevano F, Zara F. (2006) A novel SCN2A mutation in family with benign familial infantile seizures. Epilepsia, 47 (1): 218-20. [PMID:16417554]

37. Stühmer W, Methfessel C, Sakmann B, Noda M, Numa S. (1987) Patch clamp characterization of sodium channels expressed from rat brain cDNA. Eur. Biophys. J., 14 (3): 131-8. [PMID:2435540]

38. Sutkowski EM, Catterall WA. (1990) Beta 1 subunits of sodium channels. Studies with subunit-specific antibodies. J. Biol. Chem., 265 (21): 12393-9. [PMID:2165060]

39. Westenbroek RE, Merrick DK, Catterall WA. (1989) Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons. Neuron, 3 (6): 695-704. [PMID:2561976]

40. Whitaker WR, Clare JJ, Powell AJ, Chen YH, Faull RL, Emson PC. (2000) Distribution of voltage-gated sodium channel alpha-subunit and beta-subunit mRNAs in human hippocampal formation, cortex, and cerebellum. J. Comp. Neurol., 422 (1): 123-39. [PMID:10842222]

41. Wilson MJ, Yoshikami D, Azam L, Gajewiak J, Olivera BM, Bulaj G, Zhang MM. (2011) μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc. Natl. Acad. Sci. U.S.A., 108 (25): 10302-7. [PMID:21652775]

42. Wollner DA, Messner DJ, Catterall WA. (1987) Beta 2 subunits of sodium channels from vertebrate brain. Studies with subunit-specific antibodies. J. Biol. Chem., 262 (30): 14709-15. [PMID:2444590]

43. Xie X, Lancaster B, Peakman T, Garthwaite J. (1995) Interaction of the antiepileptic drug lamotrigine with recombinant rat brain type IIA Na+ channels and with native Na+ channels in rat hippocampal neurones. Pflugers Arch., 430 (3): 437-46. [PMID:7491269]

44. Xu R, Thomas EA, Jenkins M, Gazina EV, Chiu C, Heron SE, Mulley JC, Scheffer IE, Berkovic SF, Petrou S. (2007) A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel. Mol. Cell. Neurosci., 35 (2): 292-301. [PMID:17467289]

45. Yamaji N, Little MJ, Nishio H, Billen B, Villegas E, Nishiuchi Y, Tytgat J, Nicholson GM, Corzo G. (2009) Synthesis, solution structure, and phylum selectivity of a spider delta-toxin that slows inactivation of specific voltage-gated sodium channel subtypes. J. Biol. Chem., 284 (36): 24568-82. [PMID:19592486]

46. Yu FH, Westenbroek RE, Silos-Santiago I, McCormick KA, Lawson D, Ge P, Ferriera H, Lilly J, DiStefano PS, Catterall WA, Scheuer T, Curtis R. (2003) Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J. Neurosci., 23 (20): 7577-85. [PMID:12930796]

47. Zaharenko AJ, Schiavon E, Ferreira Jr WA, Lecchi M, de Freitas JC, Richardson M, Wanke E. (2012) Characterization of selectivity and pharmacophores of type 1 sea anemone toxins by screening seven Na(v) sodium channel isoforms. Peptides, 34 (1): 158-67. [PMID:21802465]

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William A. Catterall, Alan L. Goldin, Stephen G. Waxman.
Voltage-gated sodium channels: Nav1.2. Last modified on 26/06/2018. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=579.