Differential Modulation of Sodium Channel Gating and Persistent Sodium Currents by the β1, β2, and β3 Subunits

Abstract

Brain sodium channels are complexes of a pore-forming α subunit with auxiliary β subunits, which are transmembrane proteins that modulate α subunit function. The newly cloned β3 subunit is shown to be expressed broadly in neurons in the central and peripheral nervous systems, but not in glia and most nonneuronal cells. β1, β2, and β3 subunits are coexpressed in many neuronal cell types, but are differentially expressed in ventromedial nucleus of the thalamus, brain stem nuclei, cerebellar Purkinje cells, and dorsal root ganglion cells. Coexpression of β1, β2, and β3 subunits with Nav1.2a α subunits in the tsA-201 subclone of HEK293 cells shifts sodium channel activation and inactivation to more positive membrane potentials. However, β3 is unique in causing increased persistent sodium currents. Because persistent sodium currents are thought to amplify summation of synaptic inputs, expression of this subunit would increase the excitability of specific groups of neurons to all of their inputs.