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

Abstract

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 Nav1.7, a TTX-sensitive Na+ channel widely expressed in both small and large DRG neurons. Nav1.7 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 Nav1.7 formed stable complexes with the β1- β3 subunits in vivo and that Nav1.7 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 Nav1.7 channels. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.