Independent and joint modulation of rat Nav1.6 voltage-gated sodium channels by coexpression with the auxiliary β1 and β2 subunits

► The β1 and β2 subunits exert unique effects on Nav1.6 voltage-gated sodium channels. ► The β1 subunit speeds inactivation and stabilizes channels on repeated depolarization. ► The β2 subunit retarded inactivation and shifted the voltage dependence of activation. ► Some joint effects of the β1 and β2 subunits do not reflect their individual effects. ► Both β subunits are required to express currents typical of native Nav1.6 channels.