The adult rat brain beta 1 subunit modifies activation and inactivation gating of multiple sodium channel alpha subunits.

The sodium channel from adult rat brain consists of a high molecular weight alpha subunit associated with low molecular weight subunits termed beta 1 and beta 2. Coexpression of beta 1 accelerates the macroscopic kinetics of inactivation of adult rat brain IIA, embryonic rat brain III, and rat skeletal muscle SkM1 sodium channel alpha subunits. In addition, beta 1 accelerates the kinetics of activation, as observed with a non-inactivating rat brain IIA mutant. Analysis of the effects of beta 1 on the slowly inactivating brain III alpha subunit shows that both of these effects may be the result of changes in the modal gating behavior of the sodium channels expressed in Xenopus oocytes. Although the adult rat brain beta 1 subunit modulates the functional properties of rat skeletal muscle and embryonic brain III sodium channel alpha subunits, mRNA hybridizing to a beta 1 subunit cDNA probe was only faintly detected in RNA from adult skeletal muscle and not at all in RNA from embryonic brains. These results indicate that the adult rat brain beta 1 subunit can modify the modal gating properties of sodium channel alpha subunits with which it is not normally associated, suggesting the presence of conserved domains for interactions between the different alpha and beta 1 subunits of the sodium channel.