Differential expression of sodium channel β subunits in dorsal root ganglion sensory neurons

The small-diameter (<25 μm) and large-diameter (>30 μm) sensory neurons of the dorsal root ganglion (DRG) express distinct combinations of tetrodotoxin sensitive and tetrodotoxin-resistant Na⁺ channels that underlie the unique electrical properties of these neurons. In vivo, these Na⁺ channels are formed as complexes of pore-forming α and auxiliary β subunits. The goal of this study was to investigate the expression of β subunits in DRG sensory neurons. Quantitative single-cell RT-PCR revealed that β subunit mRNA is differentially expressed in small (β₂ and β₃) and large (β₁ and β₂) DRG neurons. This raises the possibility that β subunit availability and Na⁺ channel composition and functional regulation may differ in these subpopulations of sensory neurons. To further explore these possibilities, we quantitatively compared the mRNA expression of the β subunit with that of Na_v1.7, a TTX-sensitive Na⁺ channel widely expressed in both small and large DRG neurons. Na_v1.7 and β subunit mRNAs were significantly correlated in small (β₂ and β₃) and large (β₁ and β₂) DRG neurons, indicating that these subunits are coexpressed in the same populations. Co-immunoprecipitation and immunocytochemistry indicated that Na_v1.7 formed stable complexes with the β₁- β₃ subunits in vivo and that Na_v1.7 and β₃ co-localized within the plasma membranes of small DRG neurons. Heterologous expression studies showed that β₃ induced a hyperpolarizing shift in Nav1.7 activation, whereas β₁ produced a depolarizing shift in inactivation and faster recovery. The data indicate that β₃ and β₁ subunits are preferentially expressed in small and large DRG neurons, respectively, and that these auxiliary subunits differentially regulate the gating properties of Na_v1.7 channels.