Nav1.7 is the predominant sodium channel in rodent olfactory sensory neurons

Background: Voltage-gated sodium channel Na(v)1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic neurons within the peripheral nervous system. Homozygous or compound heterozygous loss-of-function mutations in SCN9A, the gene which encodes Na(v)1.7, cause congenital insensitivity to pain (CIP) accompanied by anosmia. Global knock-out of Na(v)1.7 in mice is neonatal lethal reportedly from starvation, suggesting anosmia. These findings led us to hypothesize that Na(v)1.7 is the main sodium channel in the peripheral olfactory sensory neurons (OSN, also known as olfactory receptor neurons). Methods: We used multiplex PCR-restriction enzyme polymorphism, in situ hybridization and immunohistochemistry to determine the identity of sodium channels in rodent OSNs. Results: We show here that Na(v)1.7 is the predominant sodium channel transcript, with low abundance of other sodium channel transcripts, in olfactory epithelium from rat and mouse. Our in situ hybridization data show that Na(v)1.7 transcripts are present in rat OSNs. Immunostaining of Na(v)1.7 and Na(v)1.6 channels in rat shows a complementary accumulation pattern with Na(v)1.7 in peripheral presynaptic OSN axons, and Na(v)1.6 primarily in postsynaptic cells and their dendrites in the glomeruli of the olfactory bulb within the central nervous system. Conclusions: Our data show that Na(v)1.7 is the dominant sodium channel in rat and mouse OSN, and may explain anosmia in Na(v)1.7 null mouse and patients with Na(v)1.7-related CIP.