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.
Highlights
Excitable cells such as neurons and myocytes communicate via action potentials, and voltage-gated sodium (Nav) channels play an essential role in this process
An earlier review described Nav channel b subunits as ‘anything but auxiliary’ [99]. We agree with this sentiment, and we emphasize the integration of the b subunits with other Nav channel components
As a case in point, we note the current interest in the pharmacological potential of animal toxins that target Nav channels [100]
Summary
An earlier review described Nav channel b subunits as ‘anything but auxiliary’ [99]. We agree with this sentiment, and we emphasize the integration of the b subunits with other Nav channel components. The binding affinity of these toxins for Nav channels is increased by the presence of specific b subunits [101,102]. This raises interesting questions about the nature of the toxin-binding sites. We suggest that screening assays for such toxins and drugs should include, wherever possible, the relevant b 10 subunit(s) for the Nav channels in question. These are interesting times for Nav channel b subunit research. The new results from X-ray crystallography and molecular imaging provide the first detailed look at the molecules, and will encourage both the generation of detailed functional hypotheses and their experimental testing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
