Differential Expression of Sodium Channel β Subunits in Dorsal Root Ganglion Sensory Neurons

The small-diameter (<25 mu m) and large-diameter (>30 mu m) 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 alpha and auxiliary beta subunits. The goal of this study was to investigate the expression of beta subunits in DRG sensory neurons. Quantitative single-cell RTPCR revealed that beta subunit mRNA is differentially expressed in small (beta(2) and beta(3)) and large (beta(1) and beta(2)) DRG neurons. This raises the possibility that beta 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 beta subunit with that of Na(v)1.7, a TTX-sensitive Na+ channel widely expressed in both small and large DRG neurons. Na(v)1.7 and beta subunit mRNAs were significantly correlated in small (beta(2) and beta(3)) and large (beta(1) and beta(2)) DRG neurons, indicating that these subunits are coexpressed in the same populations. Co-immunoprecipitation and immunocytochemistry indicated that Na(v)1.7 formed stable complexes with the beta(1)-beta(3) subunits in vivo and that Na(v)1.7 and beta(3) co-localized within the plasma membranes of small DRG neurons. Heterologous expression studies showed that beta(3) induced a hyperpolarizing shift in Na(v)1.7 activation, whereas beta(1) produced a depolarizing shift in inactivation and faster recovery. The data indicate that beta(3) and beta(1) subunits are preferentially expressed in small and large DRG neurons, respectively, and that these auxiliary subunits differentially regulate the gating properties of Na(v)1.7 channels.