• Sodium channels

    Show Compounds

    Detailed Information

    Name: SCN9A_HUMAN
    Recommended name: Sodium channel protein type 9 subunit alpha
    Alternative Names:
    • Neuroendocrine sodium channel
    • Peripheral sodium channel 1
    • Sodium channel protein type IX subunit alpha
    • Voltage-gated sodium channel subunit alpha Nav1.7
    Pubmed: 20146699
    23941888
    Uniprot ID: Q15858
    Synonyms: NENA, SCN9A
    Sequence length: 1988 AA.
    BindingDB: Q15858
    Kegg: hsa:6335
    Drug Bank: Sodium Channel
    Chembl: CHEMBL4296
    Prosite: PS50096
    Pfam: PF11933
    GeneID: 6335
    Ensembl: ENST00000409435
    Phosphosite: Q15858
    RefSeq: NP_002968.1
    UniGene: 439145
    NIG genetics: SCN9A
    OMIM: 603415
    WikiGenes: 6335
    IUPHAR: SCN9A

    Voltage-gated sodium channels are activated through an action potential firing.

    Structure and Function

    There are nine pore-forming α-subunits (Nav1.1 - Nav1.9) known in mammals. Each α-subunit consists of four repeat domains each containing six membrane-spanning segments. These subunits interact with β-subunits and other proteins. Since Nav1.7, Nav1.8 and Nav1.9 are mainly expressed in peripheral neurons, it is possible to target them without affecting the central nervous system or heart. Especially Nav1.7 was found to play an important role in acute and inflammatory pain.

    Properties

    Voltage-gated sodium channels represent the target for local anesthetic agents. It is challenging to find selective targets of sodium channels in the pain pathway. Genotyping of families suffering from congenital indifference to pain identified mutations in gene coding for Nav1.7 channels. Other subtypes of voltage-gated sodium channels (Nav1.3, Nav1.8, Nav1.9) play also important roles, but to date it is difficult to develop subtype-specific sodium-channel blocking agents.

    Pain-related diseases

    Nav1.7 is important for the perception of pain. Mutations in the SCN9A gene showed several effects on the expression of the α-subunit. Patients without Nav1.7 showed insensitivity to pain. People suffering from erythromelalgia have a mutation of the SCN9A gene, which - in contrast - leads to extremely high Nav1.7-activity. This causes attacks of burning pain and elevated skin temperature.

    Open Channel Conformation of a Voltage Gated Sodium Channel (Ref)
    4F4L
    Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel NaV1.5 (Ref)
    2L53