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 [12]. 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 [16]. 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 [16]. 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) [11] and approved by the NC-IUPHAR Subcommittee on sodium channels (Catterall et al., 2005, [4]).

Sodium channels are also blocked by local anaesthetic agents, antiarrythmic drugs and antiepileptic drugs. In general, these drugs are not highly selective among channel subtypes. There are two clear functional fingerprints for distinguishing different subtypes. These are sensitivity to tetrodotoxin (Na_V1.5, Na_V1.8 and Na_V1.9 are much less sensitive to block) and rate of fast inactivation (Na_V1.8 and particularly Na_V1.9 inactivate more slowly). All sodium channels also have a slow inactivation process that is engaged during long depolarizations (>100 ms) or repetitive trains of stimuli. All sodium channel subtypes are blocked by intracellular QX-314.

* Key recommended reading is highlighted with an asterisk

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Subcommittee members: William A. Catterall (Chairperson) (1946-2024) Department of Pharmacology University of Washington Mailstop 357280 Seattle WA 98195 USA Alan L. Goldin Professor, Department of Microbiology & Molecular Genetics Director, Medical Scientist Training Program Associate Vice Chancellor for Academic Affairs Health Affairs | University of California, Irvine 240 Medical Sciences B, Irvine, CA 92697-4025 Vice Chancellor’s Office: 264 Irvine Hall Faculty Office: 251 Medical Sciences C Stephen G. Waxman Department of Neurology P.O. Box 208018, 708 LCI 15 York Street New Haven CT, 06520 USA