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 w eight alpha subunit associated with low molecular weight subunits term ed beta(1) and beta(2). Coexpression of beta(1) accelerates the macros copic kinetics of inactivation of adult rat brain IIA, embryonic rat b rain III, and rat skeletal muscle SkM1 sodium channel alpha subunits. In addition, beta(1) accelerates the kinetics of activation, as observ ed with a non-inactivating rat brain IIA. mutant. Analysis of the effe cts of beta(1) on the slowly inactivating brain III alpha subunit show s 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 chann el alpha subunits, mRNA hybridizing to a beta(1) subunit cDNA probe wa s only faintly detected in RNA from adult skeletal muscle and not at a ll in RNA from embryonic brains. These results indicate that the adult rat brain beta(1) subunit can modify the modal gating properties of s odium 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.