Voltage gated sodium channel, alpha-4 subunit (IPR028826)
Short name: Na_channel_a4su
- Voltage gated sodium channel, alpha subunit (IPR001696)
- Voltage gated sodium channel, alpha-4 subunit (IPR028826)
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.
This entry represents the voltage-gated sodium channel alpha-4 subunit (Nav1.4, also known as SCN4A). Nav1.4 is expressed in skeletal muscle [PMID: 16919992]. Mutations in Nav1.4 gene cause several diseases in humans, such as Paramyotonia congenita of von Eulenburg (PMC), Myotonia SCN4A-related (MYOSCN4A) and Periodic paralysis hyperkalemic (HYPP) [PMID: 10369308, PMID: 19118277, PMID: 11591859, PMID: 18046642, PMID: 20076800, PMID: 12766226].
This entry also includes protein para from fruit flies [PMID: 2550145].
- PTHR10037:SF223 (PTHR10037:SF223)