Voltage gated sodium channel, alpha-5 subunit (IPR008053)

Short name: Na_channel_a5su

Overlapping homologous superfamilies


Family relationships


Voltage-dependent sodium channels are transmembrane (TM) proteins responsible for the depolarising phase of the action potential in most electrically excitable cells [PMID: 1317577]. They may exist in 3 states [PMID: 1323284]: the resting state, where the channel is closed; the activated state, where the channel is open; and the inactivated state, where the channel is closed and refractory to opening. Several different structurally and functionally distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents found in excitable tissues.

The structure of sodium channels is based on 4 internal repeats of a 6-helix bundle [PMID: 6209577] (in which 5 of the membrane-spanning segments are hydrophobic and the other is positively charged), forming a 24-helical bundle. The charged segments are believed to be localised within clusters formed by their 5 hydrophobic neighbours: it is postulated that the charged domain may be the voltage sensor region, possibly moving outward on depolarisation, causing a conformational change. This model [PMID: 6209577] contrasts with another [PMID: 1323284], in which the TM segments are juxtaposed octagonally. The basic structural motif (the 6-helix bundle) is also found in potassium and calcium channel alpha subunits.

The SCN5A gene encodes the NaH1 channel and is expressed in cardiac muscle, foetal skeletal muscle and denervated adult skeletal muscle. Mutations in the SCN5A gene affect the function of NaH1 channels in the heart and are one of the three causes of Long QT syndrome, an inherited cardiac arrhythmia that can cause abrupt loss of consciousness, seizures and sudden death [PMID: 7889574]; it is also associated with Brugada syndrome [PMID: 10358800] and conduction system disease [PMID: 10471492].

This entry represents the alpha 5 subunits and distinguishes them from other members of the voltage-gated Na+ channel superfamily. For entries containing other members of this superfamily see IPR008051, IPR008052, IPR008054.

GO terms

Biological Process

GO:0006814 sodium ion transport

Molecular Function

GO:0005248 voltage-gated sodium channel activity

Cellular Component

GO:0001518 voltage-gated sodium channel complex

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.