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

The voltage-sensitive sodium channel confers electrical excitability on neurons, a fundamental property required for higher processes including cognition. The ion-conducting alpha-subunit of the channel is regulated by two known auxiliary subunits, beta 1 and beta 2. We have identified rat and human forms of an additional subunit, beta 3. It is most closely related to beta 1 and is the product of a separate gene localized to human chromosome 11q23.3. When expressed in Xenopus oocytes, beta 3 inactivates sodium channel opening more slowly than beta 1 does. Structural modeling has identified an amino acid residue in the putative alpha-subunit binding site of beta 3 that may play a role in this difference. The expression of beta 3 within the central nervous system differs significantly from beta 1. Our results strongly suggest that beta 3 performs a distinct neurophysiological function.