More information on this family may be found on the IUPHAR-DB family and introduction pages.
Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise of one pore-forming α subunit, which may be associated with either one or two β subunits [3]. α-Subunits consist of four homologous domains (I–IV), each containing six transmembrane segments (S1–S6) and a pore-forming loop. The positively charged fourth transmembrane segment (S4) acts as a voltage sensor and is involved in channel gating. The crystal structure of the bacterial NavAb channel has revealed a number of novel structural features compared to earlier potassium channel structures including a short selectivity filter with ion selectivity determined by interactions with glutamate side chains [4]. Interestingly, the pore region is penetrated by fatty acyl chains that extend into the central cavity which may allow the entry of small, hydrophobic pore-blocking drugs [4]. Auxiliary β1, β2, β3 and β4 subunits consist of a large extracellular N-terminal domain, a single transmembrane segment and a shorter cytoplasmic domain.
The nomenclature for sodium channels was proposed by Goldin et al., (2000) [2] and approved by the NC-IUPHAR subcommittee on sodium channels (Catterall et al., 2005, [1]).
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Subunits 
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Andavan, GS; Lemmens-Gruber, R. (2011) Voltage-gated sodium channels: mutations, channelopathies and targets. Curr. Med. Chem., 18 (3): 377-97. [PMID:21143119]
Baker, MD; Wood, JN. (2001) Involvement of Na+ channels in pain pathways. Trends Pharmacol. Sci., 22 (1): 27-31. [PMID:11165669]
Bean, BP. (2007) The action potential in mammalian central neurons. Nat. Rev. Neurosci., 8 (6): 451-65. [PMID:17514198]
Cantrell, AR; Catterall, WA. (2001) Neuromodulation of Na+ channels: an unexpected form of cellular plasticity. Nat. Rev. Neurosci., 2 (6): 397-407. [PMID:11389473]
Catterall, WA. (1995) Structure and function of voltage-gated ion channels. Annu. Rev. Biochem., 64: 493-531. [PMID:7574491]
Catterall, WA. (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron, 26 (1): 13-25. [PMID:10798388]
Catterall, WA; Dib-Hajj, S; Meisler, MH; Pietrobon, D. (2008) Inherited neuronal ion channelopathies: new windows on complex neurological diseases. J. Neurosci., 28 (46): 11768-77. [PMID:19005038]
Catterall, WA; Goldin, AL; Waxman, SG. (2005) International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol. Rev., 57 (4): 397-409. [PMID:16382098]
Dib-Hajj, SD; Cummins, TR; Black, JA; Waxman, SG. (2010) Sodium channels in normal and pathological pain. Annu. Rev. Neurosci., 33: 325-47. [PMID:20367448]
England, S; de Groot, MJ. (2009) Subtype-selective targeting of voltage-gated sodium channels. Br. J. Pharmacol., 158 (6): 1413-25. [PMID:19845672]
Fozzard, HA; Hanck, DA. (1996) Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms. Physiol. Rev., 76 (3): 887-926. [PMID:8757791]
Fozzard, HA; Lee, PJ; Lipkind, GM. (2005) Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr. Pharm. Des., 11 (21): 2671-86. [PMID:16101448]
George, AL. (2005) Inherited disorders of voltage-gated sodium channels. J. Clin. Invest., 115 (8): 1990-9. [PMID:16075039]
Goldin, AL. (2001) Resurgence of sodium channel research. Annu. Rev. Physiol., 63: 871-94. [PMID:11181979]
Han, TS; Teichert, RW; Olivera, BM; Bulaj, G. (2008) Conus venoms - a rich source of peptide-based therapeutics. Curr. Pharm. Des., 14 (24): 2462-79. [PMID:18781995]
Isom, LL. (2001) Sodium channel beta subunits: anything but auxiliary. Neuroscientist, 7 (1): 42-54. [PMID:11486343]
Kyle, DJ; Ilyin, VI. (2007) Sodium channel blockers. J. Med. Chem., 50 (11): 2583-8. [PMID:17489575]
Lai, J; Porreca, F; Hunter, JC; Gold, MS. (2004) Voltage-gated sodium channels and hyperalgesia. Annu. Rev. Pharmacol. Toxicol., 44: 371-97. [PMID:14744251]
Lewis, RJ; Garcia, ML. (2003) Therapeutic potential of venom peptides. Nat Rev Drug Discov, 2 (10): 790-802. [PMID:14526382]
Mantegazza, M; Curia, G; Biagini, G; Ragsdale, DS; Avoli, M. (2010) Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol, 9 (4): 413-24. [PMID:20298965]
Matulenko, MA; Scanio, MJ; Kort, ME. (2009) Voltage-gated sodium channel blockers for the treatment of chronic pain. Curr Top Med Chem, 9 (4): 362-76. [PMID:19442207]
Priest, BT; Kaczorowski, GJ. (2007) Blocking sodium channels to treat neuropathic pain. Expert Opin. Ther. Targets, 11 (3): 291-306. [PMID:17298289]
Priestley, T. (2004) Voltage-gated sodium channels and pain. Curr Drug Targets CNS Neurol Disord, 3 (6): 441-56. [PMID:15578963]
Terlau, H; Olivera, BM. (2004) Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol. Rev., 84 (1): 41-68. [PMID:14715910]
Trimmer, JS; Rhodes, KJ. (2004) Localization of voltage-gated ion channels in mammalian brain. Annu. Rev. Physiol., 66: 477-519. [PMID:14977411]
Wood, JN; Boorman, J. (2005) Voltage-gated sodium channel blockers; target validation and therapeutic potential. Curr Top Med Chem, 5 (6): 529-37. [PMID:16022675]
Yu, FH; Catterall, WA. (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci. STKE, 2004 (253): re15. [PMID:15467096]
1. Catterall, WA; Goldin, AL; Waxman, SG. (2005) International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol. Rev., 57 (4): 397-409. [PMID:16382098]
2. Goldin, AL; Barchi, RL; Caldwell, JH; Hofmann, F; Howe, JR; Hunter, JC; Kallen, RG; Mandel, G; Meisler, MH; Netter, YB; Noda, M; Tamkun, MM; Waxman, SG; Wood, JN; Catterall, WA. (2000) Nomenclature of voltage-gated sodium channels. Neuron, 28 (2): 365-8. [PMID:11144347]
3. Isom, LL. (2001) Sodium channel beta subunits: anything but auxiliary. Neuroscientist, 7 (1): 42-54. [PMID:11486343]
4. Payandeh, J; Scheuer, T; Zheng, N; Catterall, WA. (2011) The crystal structure of a voltage-gated sodium channel. Nature, 475 (7356): 353-8. [PMID:21743477]
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Sodium channels are also blocked by local anaesthetic agents, antiarrythmic drugs and antiepileptic drugs. There are two clear functional fingerprints for distinguishing different subtypes. These are sensitivity to tetrodotoxin (NaV1.5, NaV1.8 and NaV1.9 are much less sensitive to block) and rate of inactivation (NaV1.8 and particularly NaV1.9 inactivate more slowly).