title: A new look at sodium channel β subunits.
abstract: Voltage-gated sodium (Nav) channels are intrinsic plasma membrane proteins that initiate the action potential in electrically excitable cells. They are a major focus of research in neurobiology, structural biology, membrane biology and pharmacology. Mutations in Nav channels are implicated in a wide variety of inherited pathologies, including cardiac conduction diseases, myotonic conditions, epilepsy and chronic pain syndromes. Drugs active against Nav channels are used as local anaesthetics, anti-arrhythmics, analgesics and anti-convulsants. The Nav channels are composed of a pore-forming α subunit and associated β subunits. The β subunits are members of the immunoglobulin (Ig) domain family of cell-adhesion molecules. They modulate multiple aspects of Nav channel behaviour and play critical roles in controlling neuronal excitability. The recently published atomic resolution structures of the human β3 and β4 subunit Ig domains open a new chapter in the study of these molecules. In particular, the discovery that β3 subunits form trimers suggests that Nav channel oligomerization may contribute to the functional properties of some β subunits.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Namadurai
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
authors.forename: Nikitha R
authors.initials: NR
authors.lastname: Yereddi
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
authors.forename: Fiona S
authors.initials: FS
authors.lastname: Cusdin
authors.affiliation: Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Christopher L H
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
authors.forename: Dimitri Y
authors.initials: DY
authors.lastname: Chirgadze
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK apj10@cam.ac.uk.
authors.forename: Antony P
authors.identifier: http://orcid.org/0000-0002-2895-7387
authors.initials: AP
authors.lastname: Jackson
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D062546:Voltage-Gated Sodium Channel beta Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D062546:Voltage-Gated Sodium Channel beta Subunits
keywords: X-ray crystallography; ion channelopathies; sodium channel β subunits