β3: An additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics

• DOI: 10.1073/pnas.030362197
• Publication Date: 2002-07-26T14:37:36Z
• Authors: Kevin Morgan; Edward B. Stevens; Bhaval Shah; Peter J. Cox; Alistair K. Dixon; Kevin Lee; Robert D. Pinnock; John Hughes; Peter J. Richardson; Kenji Mizuguchi; Antony P. Jackson
• Keywords: 0301 basic medicine; 0303 health sciences; Base Sequence; Molecular Sequence Data; Chromosome Mapping; Gene Expression; PC12 Cells; Sodium Channels; Rats; Kinetics; 03 medical and health sciences; Animals; Humans; Amino Acid Sequence; Ion Channel Gating

The voltage-sensitive sodium channel confers electrical excitability on neurons, a fundamental property required for higher processes including cognition. The ion-conducting α-subunit of the channel is regulated by two known auxiliary subunits, β1 and β2. We have identified rat and human forms of an additional subunit, β3. It is most closely related to β1 and is the product of a separate gene localized to human chromosome 11q23.3. When expressed in Xenopus oocytes, β3 inactivates sodium channel opening more slowly than β1 does. Structural modeling has identified an amino acid residue in the putative α-subunit binding site of β3 that may play a role in this difference. The expression of β3 within the central nervous system differs significantly from β1. Our results strongly suggest that β3 performs a distinct neurophysiological function.