FUNCTIONAL COEXPRESSION OF THE BETA-1 AND TYPE IIA ALPHA-SUBUNITS OF SODIUM-CHANNELS IN A MAMMALIAN-CELL LINE

Brain sodium channels are a complex of alpha (260 kDa), beta 1 (36 kDa ), and beta 2 (33 kDa) subunits, a subunits are functional as voltage- gated sodium channels by themselves. When expressed in Xenopus oocytes , beta 1 subunits accelerate the time course of sodium channel activat ion and inactivation by shifting them to a fast gating mode, but alpha subunits expressed alone in mammalian cells activate and inactivate r apidly without co-expression of beta 1 subunits. In these experiments, we show that the Chinese hamster cell lines CHO and 1610 do not expre ss endogenous beta 1 subunits as determined by Northern blotting, immu noblotting, and assay for beta 1 subunit function by expression of cel lular mRNA in Xenopus oocytes. alpha subunits expressed alone in stabl e lines of these cells activate and inactivate rapidly. Co-expression of beta 1 subunits increases the level of sodium channels 2- to 4-fold as determined hom saxitoxin binding, but does not affect the K-d for saxitoxin. Co-expression of beta 1 subunits also shifts the voltage de pendence of sodium channel inactivation to more negative membrane pote ntials by 10 to 12 mV and shifts the voltage dependence of channel act ivation to more negative membrane potentials by 2 to 11 mV. These effe cts of beta 1 subunits on sodium channel function in mammalian cells m ay be physiologically important determinants of sodium channel functio n in vivo.