image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing. 

Nav1.4

Family: Voltage-gated sodium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Activators
Gating Inhibitors
Pore Blockers
Tissue Distribution
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 1 1836 17q23-25 SCN4A sodium channel, voltage-gated, type IV, alpha subunit 2,11,65
Mouse 24 1 1841 11 E1 Scn4a sodium channel, voltage-gated, type IV, alpha 1,69
Rat 24 1 1840 10q32.1 Scn4a sodium channel, voltage-gated, type IV, alpha subunit 1,58
Previous and Unofficial Names
SkM1
μ1
Nav1.4
HYKPP
HYPP
NCHVS
microI
Sodium channel voltage-gated type IV alpha polypeptide
Sodium channel, voltage-gated, type IV, alpha polypeptide
mu-1
sodium channel protein skeletal muscle subunit alpha
sodium channel protein type 4 subunit alpha
sodium channel protein type IV subunit alpha
sodium channel voltage-gated type 4 alpha polypeptide
sodium channel, voltage-gated, type 4, alpha polypeptide
sodium channel, voltage-gated, type 4, alpha subunit
sodium channel, voltage-gated, type IV, alpha
voltage-gated sodium channel subunit alpha Nav1.4
mH2
Database Links
ChEMBL Target 18043 (Hs), 12605 (Rn)
DrugBank Target 3804 (Hs)
Ensembl ENSG00000007314 (Hs), ENSMUSG00000001027 (Mm), ENSRNOG00000012134 (Rn)
Entrez Gene 6329 (Hs), 110880 (Mm), 25722 (Rn)
GeneCards SCN4A (Hs)
GenitoUrinary Development Molecular Anatomy Project Scn4a (Mm)
HomoloGene 283 (Hs)
Human Protein Reference Database 04912 (Hs)
InterPro P35499 (Hs), Q9ER60 (Mm), P15390 (Rn)
KEGG Gene hsa:6329 (Hs), mmu:110880 (Mm), rno:25722 (Rn)
OMIM 603967 (Hs)
Orphanet Gene ORPHA118507 (Hs)
PharmGKB Gene PA35006 (Hs)
PhosphoSitePlus P35499 (Hs), Q9ER60 (Mm)
Protein Ontology (PRO) PRO:000002100 (Hs)
RefSeq Nucleotide NM_000334 (Hs), NM_133199 (Mm), NM_013178 (Rn)
RefSeq Protein NP_000325 (Hs), NP_573462 (Mm), NP_037310 (Rn)
TreeFam ENSG00000007314 (Hs), ENSMUSG00000001027 (Mm), ENSRNOG00000012134 (Rn)
UniGene Hs. 46038 (Hs)
UniProt P35499 (Hs), Q9ER60 (Mm), P15390 (Rn)
Wikipedia Nav1.4
Voltage-gated sodium channels
Search for 3D structures on the PDB
Search by keyword: Voltage-gated sodium channels Nav1.4 Search by accession number: P15390, P35499, Q9ER60
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
β1 14,24
Other Associated Proteins
Name References
Not determined
Ion Selectivity and Conductance
Species:  Rat
Rank order:  Na+ > K+ > Rb+ > Cs+
References:  57
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -36.0 – -29.6 (median: -33.0) - 25,38 HEK-293, tsA-201 Human
Inactivation  -80.0 – -72.8 (median: -76.0) 0.6 25,38
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -32.7 – -22.8 (median: -30.0) - 16,27,64,66 HEK 293 cells. Rat
Inactivation  -88.5 – -66.1 (median: -75.0) - 16,27,64,66
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -25.9 - 6 CHO cells. Human
Inactivation  -56.0 1.1 6
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
grayanotoxin Rn - - 3x10-4 -120.0 26
veratridine Rn - - 2x10-4 -100.0 67
batrachotoxin Rn - - 5x10-6 -100.0 67
β-scorpion toxin TiTXγ Rn - - 5x10-8 -100.0 34
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
AFT-II Hs 7.5 pEC50 - -80.0 42
ATX-II Hs 7.0 – 7.3 pEC50 - -100.0 – -80.0 12,42
Bc-III Hs 6.1 pEC50 - -80.0 42
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
saxitoxin Rn 8.4 pIC50 - -100.0 44
tetrodotoxin Rn 8.3 pIC50 - -120.0 59
tetrodotoxin Hs 7.6 pIC50 - -120.0 11
μ-conotoxin GIIIA Rn 7.3 – 7.7 pIC50 - -120.0 – -100.0 13,53
μ-conotoxin PIIIA Rn 7.4 pIC50 - -120.0 53
μ-conotoxin GIIIA Hs 5.9 pIC50 - -100.0 11
mexilitine Hs 3.4 pIC50 - -140.0 63
lidocaine Rn 2.7 pIC50 - -130.0 33
View species-specific pore blocker tables
Tissue Distribution
Skeletal muscle
Species:  Rat
Technique:  RT-PCR
References:  56
Skeletal muscle
Species:  Rat
Technique:  Northern Blot
References:  58
Physiological Functions
Action potential initiation and transmission
Species:  Human
Tissue:  skeletal muscle
References:  20,59
Physiological Functions Comments
The stated role of Nv1.4 has been reported for mamalian skeletal muscles [58-59].
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0002106 abnormal muscle physiology PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0002106 abnormal muscle physiology PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0003084 abnormal skeletal muscle fiber morphology PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0003084 abnormal skeletal muscle fiber morphology PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0003084 abnormal skeletal muscle fiber morphology PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0003084 abnormal skeletal muscle fiber morphology PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0001262 decreased body weight PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0001262 decreased body weight PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0008770 decreased survivor rate PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0008770 decreased survivor rate PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0003157 impaired muscle relaxation PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0003157 impaired muscle relaxation PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0002841 impaired skeletal muscle contractility PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0002841 impaired skeletal muscle contractility PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0004037 increased muscle relaxation PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0004037 increased muscle relaxation PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0009403 increased variability of skeletal muscle fiber size PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0009403 increased variability of skeletal muscle fiber size PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0009403 increased variability of skeletal muscle fiber size PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0009403 increased variability of skeletal muscle fiber size PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0001513 limb grasping PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0001513 limb grasping PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0003646 muscle fatigue PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0003646 muscle fatigue PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0000747 muscle weakness PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0000747 muscle weakness PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0000747 muscle weakness PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0000747 muscle weakness PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0000751 myopathy PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0000751 myopathy PMID: 18317596 
Scn4a+|Scn4atm1Ljh Scn4atm1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0000751 myopathy PMID: 18317596 
Scn4a+|Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4a+
B6.129S4-Scn4a		 MGI:98250  MP:0000751 myopathy PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0002081 perinatal lethality PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0002081 perinatal lethality PMID: 18317596 
Scn4atm1.1Ljh Scn4atm1.1Ljh/Scn4atm1.1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0009417 skeletal muscle atrophy PMID: 18317596 
Scn4atm1Ljh Scn4atm1Ljh/Scn4atm1Ljh
B6.129S4-Scn4a		 MGI:98250  MP:0009417 skeletal muscle atrophy PMID: 18317596 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Congenital Myasthenic Syndrome
OMIM:  608931
References:  60
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human V1442E 60
Disease:  Paramyotonia Congenita (PMC)
OMIM:  168300
Orphanet:  684
References:  9,19,29
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human F1473S 17
Missense Human G1456E 9
Missense Human R1448S 9
Missense Human R1448P 32
Missense Human R1448H 47
Missense Human R1448C 47
Missense Human L1443R 46
Missense Human T1313M 47
Missense Human L266V 68
Missense Human V1293I 21
Missense Human N1297K 18
Missense Human T1313M 15
Missense Human T1313A 7
Missense Human M1370V 41
Missense Human I1393T 3
Missense Human R1448S 5
Missense Human V1458F 30
Disease:  Hyperkalemic Periodic Paralysis (HyperPP)
OMIM:  170500
Orphanet:  682
References:  9,19,29
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human M1592V 39,51
Missense Human I1495F 9
Missense Human M1493I 9
Missense Human I1490L 9
Missense Human P1158S 9
Missense Human A1156T 9,29
Missense Human T704M 39,48
Missense Human I693T 9
Missense Human L689I 9
Missense Human L689V 4
Missense Human M1360V 62
Disease:  Potassium-Aggravated Myotonia (PAM)
OMIM:  608390
Orphanet:  99734, 99735, 99736
References:  9,19,29
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human V1589M 23
Missense Human G1306V 31,37
Missense Human G1306A 31
Missense Human I1160V 49
Missense Human S804F 36,50
Missense Human V445M 52
Missense Human N129K
Missense Human I141V 45
Missense Human R225W 28
Missense Human L250P 55
Missense Human G1306E 22,40
Disease:  Hypokalemic Periodic Paralysis (HypoPP)
OMIM:  613345
Orphanet:  681
References:  9,19,29
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human R672S 9,54
Missense Human R672H 9,25,54
Missense Human R672G 9,54
Missense Human R669H 8-9,54
Missense Human R222W 43
Missense Human R1132Q 10
Missense Human R1135H 35
Disease:  Postsynaptic congenital myasthenic syndrome
OMIM:  614198
Orphanet:  98913
References: 
Mutations not determined
Disease:  Normokalemic Periodic Paralysis
OMIM:  170600
References:  61
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human R675G/E/W 61
Clinically-Relevant Mutations and Pathophysiology Comments
The majority of Nav1.4 mutations in these diseases alter the inactivation properties of the channel leading to susceptability to periods of hyperactivity (causing myotonia) or inactivation (causing paralysis).

REFERENCES

Show »

1. Ambrose, C; Cheng, S; Fontaine, B; Nadeau, JH; MacDonald, M; Gusella, JF. (1992) The alpha-subunit of the skeletal muscle sodium channel is encoded proximal to Tk-1 on mouse chromosome 11. Mamm. Genome, 3 (3): 151-5. [PMID:1352160]

2. Arnestad, M; Crotti, L; Rognum, TO; Insolia, R; Pedrazzini, M; Ferrandi, C; Vege, A; Wang, DW; Rhodes, TE; George, AL; Schwartz, PJ. (2007) Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation, 115 (3): 361-7. [PMID:17210839]

3. Arzel-Hézode, M; Sternberg, D; Tabti, N; Vicart, S; Goizet, C; Eymard, B; Fontaine, B; Fournier, E. (2010) Homozygosity for dominant mutations increases severity of muscle channelopathies. Muscle Nerve, 41 (4): 470-7. [PMID:19882638]

4. Bendahhou, S; Cummins, TR; Kula, RW; Fu, YH; Ptácek, LJ. (2002) Impairment of slow inactivation as a common mechanism for periodic paralysis in DIIS4-S5. Neurology, 58 (8): 1266-72. [PMID:11971097]

5. Bendahhou, S; Cummins, TR; Kwiecinski, H; Waxman, SG; Ptácek, LJ. (1999) Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans. J. Physiol. (Lond.), 518 ( Pt 2): 337-44. [PMID:10381583]

6. Bennett, ES. (2004) Channel activation voltage alone is directly altered in an isoform-specific manner by Na(v1.4) and Na(v1.5) cytoplasmic linkers. J. Membr. Biol., 197 (3): 155-68. [PMID:15042347]

7. Bouhours, M; Sternberg, D; Davoine, CS; Ferrer, X; Willer, JC; Fontaine, B; Tabti, N. (2004) Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans. J. Physiol. (Lond.), 554 (Pt 3): 635-47. [PMID:14617673]

8. Bulman, DE; Scoggan, KA; van Oene, MD; Nicolle, MW; Hahn, AF; Tollar, LL; Ebers, GC. (1999) A novel sodium channel mutation in a family with hypokalemic periodic paralysis. Neurology, 53 (9): 1932-6. [PMID:10599760]

9. Cannon, SC. (2002) An expanding view for the molecular basis of familial periodic paralysis. Neuromuscul. Disord., 12 (6): 533-43. [PMID:12117476]

10. Carle, T; Lhuillier, L; Luce, S; Sternberg, D; Devuyst, O; Fontaine, B; Tabti, N. (2006) Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis. Biochem. Biophys. Res. Commun., 348 (2): 653-61. [PMID:16890191]

11. Chahine, M; Bennett, PB; George, AL; Horn, R. (1994) Functional expression and properties of the human skeletal muscle sodium channel. Pflugers Arch., 427 (1-2): 136-42. [PMID:8058462]

12. Chahine, M; Plante, E; Kallen, RG. (1996) Sea anemone toxin (ATX II) modulation of heart and skeletal muscle sodium channel alpha-subunits expressed in tsA201 cells. J. Membr. Biol., 152 (1): 39-48. [PMID:8660409]

13. Chen, LQ; Chahine, M; Kallen, RG; Barchi, RL; Horn, R. (1992) Chimeric study of sodium channels from rat skeletal and cardiac muscle. FEBS Lett., 309 (3): 253-7. [PMID:1325372]

14. Cohen-Armon, M; Sokolovsky, M. (1993) Evidence for involvement of the voltage-dependent Na+ channel gating in depolarization-induced activation of G-proteins. J. Biol. Chem., 268 (13): 9824-38. [PMID:8387506]

15. Dice, MS; Abbruzzese, JL; Wheeler, JT; Groome, JR; Fujimoto, E; Ruben, PC. (2004) Temperature-sensitive defects in paramyotonia congenita mutants R1448C and T1313M. Muscle Nerve, 30 (3): 277-88. [PMID:15318338]

16. Ferrera, L; Moran, O. (2006) Beta1-subunit modulates the Nav1.4 sodium channel by changing the surface charge. , 172 (2): 139-50. [PMID:16432696]

17. Fleischhauer, R; Mitrovic, N; Deymeer, F; Lehmann-Horn, F; Lerche, H. (1998) Effects of temperature and mexiletine on the F1473S Na+ channel mutation causing paramyotonia congenita. Pflugers Arch., 436 (5): 757-65. [PMID:9716710]

18. Gay, S; Dupuis, D; Faivre, L; Masurel-Paulet, A; Labenne, M; Colombani, M; Soichot, P; Huet, F; Hainque, B; Sternberg, D; et al.. (2008) Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene. Am. J. Med. Genet. A, 146 (3): 380-3. [PMID:18203179]

19. George, AL. (2005) Inherited disorders of voltage-gated sodium channels. J. Clin. Invest., 115 (8): 1990-9. [PMID:16075039]

20. George, AL; Komisarof, J; Kallen, RG; Barchi, RL. (1992) Primary structure of the adult human skeletal muscle voltage-dependent sodium channel. Ann. Neurol., 31 (2): 131-7. [PMID:1315496]

21. Green, DS; George, AL; Cannon, SC. (1998) Human sodium channel gating defects caused by missense mutations in S6 segments associated with myotonia: S804F and V1293I. J. Physiol. (Lond.), 510 ( Pt 3): 685-94. [PMID:9660885]

22. Groome, JR; Fujimoto, E; Ruben, PC. (2005) K-aggravated myotonia mutations at residue G1306 differentially alter deactivation gating of human skeletal muscle sodium channels. Cell. Mol. Neurobiol., 25 (7): 1075-92. [PMID:16392038]

23. Heine, R; Pika, U; Lehmann-Horn, F. (1993) A novel SCN4A mutation causing myotonia aggravated by cold and potassium. Hum. Mol. Genet., 2 (9): 1349-53. [PMID:8242056]

24. 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]

25. Jurkat-Rott, K; Mitrovic, N; Hang, C; Kouzmekine, A; Iaizzo, P; Herzog, J; Lerche, H; Nicole, S; Vale-Santos, J; Chauveau, D; Fontaine, B; Lehmann-Horn, F. (2000) Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc. Natl. Acad. Sci. U.S.A., 97 (17): 9549-54. [PMID:10944223]

26. Kimura, T; Yamaoka, K; Kinoshita, E; Maejima, H; Yuki, T; Yakehiro, M; Seyama, I. (2001) Novel site on sodium channel alpha-subunit responsible for the differential sensitivity of grayanotoxin in skeletal and cardiac muscle. Mol. Pharmacol., 60 (4): 865-72. [PMID:11562450]

27. Kondratiev, A; Tomaselli, GF. (2003) Altered gating and local anesthetic block mediated by residues in the I-S6 and II-S6 transmembrane segments of voltage-dependent Na+ channels. Mol. Pharmacol., 64 (3): 741-52. [PMID:12920212]

28. Lee, SC; Kim, HS; Park, YE; Choi, YC; Park, KH; Kim, DS. (2009) Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy. J Clin Neurol, 5 (4): 186-91. [PMID:20076800]

29. Lehmann-Horn, F; Jurkat-Rott, K. (1999) Voltage-gated ion channels and hereditary disease. Physiol. Rev., 79 (4): 1317-72. [PMID:10508236]

30. Lehmann-Horn, F; Rüdel, R; Ricker, K. (1993) Non-dystrophic myotonias and periodic paralyses. A European Neuromuscular Center Workshop held 4-6 October 1992, Ulm, Germany. Neuromuscul. Disord., 3 (2): 161-8. [PMID:7689382]

31. Lerche, H; Heine, R; Pika, U; George, AL; Mitrovic, N; Browatzki, M; Weiss, T; Rivet-Bastide, M; Franke, C; Lomonaco, M. (1993) Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker. J. Physiol. (Lond.), 470: 13-22. [PMID:8308722]

32. Lerche, H; Mitrovic, N; Dubowitz, V; Lehmann-Horn, F. (1996) Paramyotonia congenita: the R1448P Na+ channel mutation in adult human skeletal muscle. Ann. Neurol., 39 (5): 599-608. [PMID:8619545]

33. Makielski, JC; Limberis, J; Fan, Z; Kyle, JW. (1999) Intrinsic lidocaine affinity for Na channels expressed in Xenopus oocytes depends on alpha (hH1 vs. rSkM1) and beta 1 subunits. Cardiovasc. Res., 42 (2): 503-9. [PMID:10533585]

34. Marcotte, P; Chen, LQ; Kallen, RG; Chahine, M. (1997) Effects of Tityus serrulatus scorpion toxin gamma on voltage-gated Na+ channels. Circ. Res., 80 (3): 363-9. [PMID:9048656]

35. Matthews, E; Labrum, R; Sweeney, MG; Sud, R; Haworth, A; Chinnery, PF; Meola, G; Schorge, S; Kullmann, DM; Davis, MB; et al.. (2009) Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology, 72 (18): 1544-7. [PMID:19118277]

36. McClatchey, AI; McKenna-Yasek, D; Cros, D; Worthen, HG; Kuncl, RW; DeSilva, SM; Cornblath, DR; Gusella, JF; Brown, RH. (1992) Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. Nat. Genet., 2 (2): 148-52. [PMID:1338909]

37. McClatchey, AI; Van den Bergh, P; Pericak-Vance, MA; Raskind, W; Verellen, C; McKenna-Yasek, D; Rao, K; Haines, JL; Bird, T; Brown, RH. (1992) Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. Cell, 68 (4): 769-74. [PMID:1310898]

38. McNulty, MM; Hanck, DA. (2004) State-dependent mibefradil block of Na+ channels. Mol. Pharmacol., 66 (6): 1652-61. [PMID:15562257]

39. Miller, TM; Dias da Silva, MR; Miller, HA; Kwiecinski, H; Mendell, JR; Tawil, R; McManis, P; Griggs, RC; Angelini, C; Servidei, S; Petajan, J; Dalakas, MC; Ranum, LP; Fu, YH; Ptácek, LJ. (2004) Correlating phenotype and genotype in the periodic paralyses. Neurology, 63 (9): 1647-55. [PMID:15534250]

40. Mitrović, N; George, AL; Lerche, H; Wagner, S; Fahlke, C; Lehmann-Horn, F. (1995) Different effects on gating of three myotonia-causing mutations in the inactivation gate of the human muscle sodium channel. J. Physiol. (Lond.), 487 ( Pt 1): 107-14. [PMID:7473241]

41. Okuda, S; Kanda, F; Nishimoto, K; Sasaki, R; Chihara, K. (2001) Hyperkalemic periodic paralysis and paramyotonia congenita--a novel sodium channel mutation. J. Neurol., 248 (11): 1003-4. [PMID:11757950]

42. 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]

43. Park, YH; Kim, JB. (2010) An atypical phenotype of hypokalemic periodic paralysis caused by a mutation in the sodium channel gene SCN4A. Korean J Pediatr, 53 (10): 909-12. [PMID:21189962]

44. Penzotti, JL; Lipkind, G; Fozzard, HA; Dudley, SC. (2001) Specific neosaxitoxin interactions with the Na+ channel outer vestibule determined by mutant cycle analysis. Biophys. J., 80 (2): 698-706. [PMID:11159437]

45. Petitprez, S; Tiab, L; Chen, L; Kappeler, L; Rösler, KM; Schorderet, D; Abriel, H; Burgunder, JM. (2008) A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia. Neurology, 71 (21): 1669-75. [PMID:19015483]

46. Ptacek, LJ; Gouw, L; Kwieciński, H; McManis, P; Mendell, JR; Barohn, RJ; George, AL; Barchi, RL; Robertson, M; Leppert, MF. (1993) Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis. Ann. Neurol., 33 (3): 300-7. [PMID:8388676]

47. Ptácek, LJ; George, AL; Barchi, RL; Griggs, RC; Riggs, JE; Robertson, M; Leppert, MF. (1992) Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita. Neuron, 8 (5): 891-7. [PMID:1316765]

48. Ptácek, LJ; George, AL; Griggs, RC; Tawil, R; Kallen, RG; Barchi, RL; Robertson, M; Leppert, MF. (1991) Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell, 67 (5): 1021-7. [PMID:1659948]

49. Ptáĉek, LJ; Tawil, R; Griggs, RC; Meola, G; McManis, P; Barohn, RJ; Mendell, JR; Harris, C; Spitzer, R; Santiago, F. (1994) Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis. Neurology, 44 (8): 1500-3. [PMID:8058156]

50. Ricker, K; Moxley, RT; Heine, R; Lehmann-Horn, F. (1994) Myotonia fluctuans. A third type of muscle sodium channel disease. Arch. Neurol., 51 (11): 1095-102. [PMID:7980103]

51. Rojas, CV; Wang, JZ; Schwartz, LS; Hoffman, EP; Powell, BR; Brown, RH. (1991) A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis. Nature, 354 (6352): 387-9. [PMID:1659668]

52. Rosenbohm, A; Rüdel, R; Fahlke, C. (1999) Regulation of the human skeletal muscle chloride channel hClC-1 by protein kinase C. J. Physiol. (Lond.), 514 ( Pt 3): 677-85. [PMID:9882739]

53. Safo, P; Rosenbaum, T; Shcherbatko, A; Choi, DY; Han, E; Toledo-Aral, JJ; Olivera, BM; Brehm, P; Mandel, G. (2000) Distinction among neuronal subtypes of voltage-activated sodium channels by mu-conotoxin PIIIA. J. Neurosci., 20 (1): 76-80. [PMID:10627583]

54. Sternberg, D; Maisonobe, T; Jurkat-Rott, K; Nicole, S; Launay, E; Chauveau, D; Tabti, N; Lehmann-Horn, F; Hainque, B; Fontaine, B. (2001) Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain, 124 (Pt 6): 1091-9. [PMID:11353725]

55. Stunnenberg, BC; Ginjaar, HB; Trip, J; Faber, CG; van Engelen, BG; Drost, G. (2010) Isolated eyelid closure myotonia in two families with sodium channel myotonia. Neurogenetics, 11 (2): 257-60. [PMID:19876661]

56. Sun, W; Cohen, SA; Barchi, RL. (1995) Localization of epitopes for monoclonal antibodies directed against the adult rat skeletal muscle sodium channel (rSkM1) using polymerase chain reaction, fusion proteins, and western blotting. Anal. Biochem., 226 (1): 188-91. [PMID:7785772]

57. Tanaka, JC; Eccleston, JF; Barchi, RL. (1983) Cation selectivity characteristics of the reconstituted voltage-dependent sodium channel purified from rat skeletal muscle sarcolemma. J. Biol. Chem., 258 (12): 7519-26. [PMID:6305944]

58. Trimmer, JS; Cooperman, SS; Agnew, WS; Mandel, G. (1990) Regulation of muscle sodium channel transcripts during development and in response to denervation. Dev. Biol., 142 (2): 360-7. [PMID:2175278]

59. Trimmer, JS; Cooperman, SS; Tomiko, SA; Zhou, JY; Crean, SM; Boyle, MB; Kallen, RG; Sheng, ZH; Barchi, RL; Sigworth, FJ. (1989) Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuron, 3 (1): 33-49. [PMID:2559760]

60. Tsujino, A; Maertens, C; Ohno, K; Shen, XM; Fukuda, T; Harper, CM; Cannon, SC; Engel, AG. (2003) Myasthenic syndrome caused by mutation of the SCN4A sodium channel. Proc. Natl. Acad. Sci. U.S.A., 100 (12): 7377-82. [PMID:12766226]

61. Vicart, S; Sternberg, D; Fournier, E; Ochsner, F; Laforet, P; Kuntzer, T; Eymard, B; Hainque, B; Fontaine, B. (2004) New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis. Neurology, 63 (11): 2120-7. [PMID:15596759]

62. Wagner, S; Lerche, H; Mitrovic, N; Heine, R; George, AL; Lehmann-Horn, F. (1997) A novel sodium channel mutation causing a hyperkalemic paralytic and paramyotonic syndrome with variable clinical expressivity. Neurology, 49 (4): 1018-25. [PMID:9339683]

63. Wang, GK; Russell, C; Wang, SY. (2004) Mexiletine block of wild-type and inactivation-deficient human skeletal muscle hNav1.4 Na+ channels. J. Physiol. (Lond.), 554 (Pt 3): 621-33. [PMID:14608007]

64. Wang, GK; Wang, SY. (2003) Veratridine block of rat skeletal muscle Nav1.4 sodium channels in the inner vestibule. J. Physiol. (Lond.), 548 (Pt 3): 667-75. [PMID:12626674]

65. Wang, JZ; Rojas, CV; Zhou, JH; Schwartz, LS; Nicholas, H; Hoffman, EP. (1992) Sequence and genomic structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q. Biochem. Biophys. Res. Commun., 182 (2): 794-801. [PMID:1310396]

66. Wang, SY; Barile, M; Wang, GK. (2001) A phenylalanine residue at segment D3-S6 in Nav1.4 voltage-gated Na(+) channels is critical for pyrethroid action. Mol. Pharmacol., 60 (3): 620-8. [PMID:11502895]

67. Wang, SY; Wang, GK. (1998) Point mutations in segment I-S6 render voltage-gated Na+ channels resistant to batrachotoxin. Proc. Natl. Acad. Sci. U.S.A., 95 (5): 2653-8. [PMID:9482942]

68. Wu, FF; Takahashi, MP; Pegoraro, E; Angelini, C; Colleselli, P; Cannon, SC; Hoffman, EP. (2001) A new mutation in a family with cold-aggravated myotonia disrupts Na(+) channel inactivation. Neurology, 56 (7): 878-84. [PMID:11294924]

69. Zimmer, T; Bollensdorff, C; Haufe, V; Birch-Hirschfeld, E; Benndorf, K. (2002) Mouse heart Na+ channels: primary structure and function of two isoforms and alternatively spliced variants. Am. J. Physiol. Heart Circ. Physiol., 282 (3): H1007-17. [PMID:11834499]

To cite this database page, please use the following:

William A. Catterall, Alan L. Goldin, Stephen G. Waxman.
Voltage-gated sodium channels: Nav1.4. Last modified on 04/01/2013. Accessed on 23/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=581.


Contact us | Print | Back to top | Help