Na+ channel protein type 4 subunit alpha; Na+ channel protein type IV subunit alpha; voltage-gated Na+ channel subunit alpha Nav1.4; Na+ channel protein skeletal muscle subunit alpha; SkM1 (SCN4A)

Function

• mediates voltage-dependent Na+ permeability of excitable membranes
• assumes opened or closed conformation in response to voltage difference across membrane
• forms a Na+-selective channel through which Na+ ions may pass in accordance with their electrochemical gradient
• muscle Na+ channels contain an alpha subunit & a smaller beta subunit
• interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 & SNTB2 (putative)

Structure

• contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) & one positively charged segment (S4)
• segment S4 is probably the voltage-sensor & is characterized by a series of positively charged amino acids at every 3rd position
• belongs to the Na+ channel family
• contains 1 IQ domain

Compartment

membrane

Expression

• may be present in both denervated & innervated skeletal muscle

Pathology

• defects in SCN4A are the cause of
  • paramyotonia congenita of von Eulenburg
  • familial periodic paralysis hypokalemic (HOKPP), hyperkalemic (HYPP), normokalemic (NKPP)
  • myotonia SCN4A-related (MYOSCN4A)
  • congenital myasthenic syndrome due to mutation in SCNA4

More general terms

• voltage-dependent Na+ channel protein alpha subunit
• glycoprotein

Additional terms

• voltage-dependent Na+ channel

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6329
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6329
• OMIM: https://mirror.omim.org/entry/168300
• OMIM: https://mirror.omim.org/entry/170400
• OMIM: https://mirror.omim.org/entry/170500
• OMIM: https://mirror.omim.org/entry/603967
• OMIM: https://mirror.omim.org/entry/608390
• UniProt: http://www.uniprot.org/uniprot/P35499.html