Distinct domains of the sodium channel beta3-subunit modulate channel-gating kinetics and subcellular location

Esther J Yu, Seong-Hoon Ko, Paul W Lenkowski, Alena Pance, Manoj K Patel, Antony P Jackson

Research output: Contribution to journalArticlepeer-review


Electrical excitability in neurons depends on the expression and activity of voltage-gated sodium channels in the neuronal plasma membrane. The ion-conducting alpha-subunit of the channel is associated with auxiliary beta-subunits of which there are four known types. In the present study, we describe the first detailed structure/function analysis of the beta3-subunit. We correlate the effect of point mutations and deletions in beta3 with the functional properties of the sodium channel and its membrane-targeting behaviour. We show that the extracellular domain influences sodium channel gating properties, but is not required for the delivery of beta3 to the plasma membrane when expressed with the alpha-subunit. In contrast, the intracellular domain is essential for correct subunit targeting. Our results reveal the crucial importance of the Cys21-Cys96 disulphide bond in maintaining the functionally correct beta3 structure and establish a role for a second putative disulphide bond (Cys2-Cys24) in modulating channel inactivation kinetics. Surprisingly, our results imply that the wild-type beta3 molecule can traverse the secretory pathway independently of the alpha-subunit.

Original languageEnglish
Pages (from-to)519-26
Number of pages8
JournalBiochemical Journal
Issue numberPt 3
Publication statusPublished - 15 Dec 2005


  • Animals
  • Base Sequence
  • CHO Cells
  • Cricetinae
  • Gene Deletion
  • Ion Channel Gating/physiology
  • Kinetics
  • Mutagenesis, Site-Directed
  • PC12 Cells
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Transport
  • Rats
  • Sodium Channels/chemistry


Dive into the research topics of 'Distinct domains of the sodium channel beta3-subunit modulate channel-gating kinetics and subcellular location'. Together they form a unique fingerprint.

Cite this