Functional Co-expression of the 1 and Type IIA Subunits of Sodium Channels in a Mammalian Cell Line

• Published in: The Journal of biological chemistry 1995-02, Vol.270 (7), p.3306
• Main Authors: Lori L. Isom, Todd Scheuer, Alice B. Brownstein, David S. Ragsdale, Brian J. Murphy, William A. Catterall
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.7.3306

Brain sodium channels are a complex of α (260 kDa), β1 (36 kDa), and β2 (33 kDa) subunits. α subunits are functional as voltage-gated sodium channels by themselves. When expressed in Xenopus oocytes, β1 subunits accelerate the time course of sodium channel activation and inactivation by shifting them to a fast gating mode, but α subunits expressed alone in mammalian cells activate and inactivate rapidly without co-expression of β1 subunits. In these experiments, we show that the Chinese hamster cell lines CHO and 1610 do not express endogenous β1 subunits as determined by Northern blotting, immunoblotting, and assay for β1 subunit function by expression of cellular mRNA in Xenopus oocytes. α subunits expressed alone in stable lines of these cells activate and inactivate rapidly. Co-expression of β1 subunits increases the level of sodium channels 2- to 4-fold as determined from saxitoxin binding, but does not affect the K for saxitoxin. Co-expression of β1 subunits also shifts the voltage dependence of sodium channel inactivation to more negative membrane potentials by 10 to 12 mV and shifts the voltage dependence of channel activation to more negative membrane potentials by 2 to 11 mV. These effects of β1 subunits on sodium channel function in mammalian cells may be physiologically important determinants of sodium channel function in vivo .