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

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

Departments of ^*Biochemistry, and ^‡Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom CB2 1QW; ^†Parke–Davis Neuroscience Research Centre, Cambridge University Forvie Site, Robinson Way, Cambridge, United Kingdom CB2 2QB

Edited by William A. Catterall, University of Washington School of Medicine, Seattle, WA, and approved December 15, 1999 (received for review August 24, 1999)

Abstract

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.

Footnotes

↵ § To whom reprint requests should be addressed. E-mail: a.p.jackson{at}bioc.cam.ac.uk.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this paper have been deposited in the EMBL database (accession nos. AJ243395 and AJ243396).
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.030362197.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.030362197
Abbreviation:

kb,

kilobase