Organization and Plasticity of Sodium Channel Expression in the Mouse Olfactory and Vomeronasal Epithelia

Abstract

To understand the molecular basis of neuronal excitation in the mammalian olfactory system, we conducted a systematic analysis of the organization of voltage-gated sodium (Nav) channel subunits in the main olfactory epithelium (MOE) and vomeronasal organ (VNO) of adult mice. We also analyzed changes in Nav channel expression during development in these two systems and during regeneration of the MOE. Quantitative PCR shows that Nav1.7 is the predominant isoform in both adult MOE and VNO. We detected pronounced immunoreactivity for Nav1.7 and Nav1.3 in axons of olfactory and vomeronasal sensory neurons (VSNs). Analysis of Nav1.2 and Nav1.6 revealed an unexpected subsystem-specific distribution. In the MOE, these Nav channels are absent from olfactory sensory neurons (OSNs) but present in non-neuronal olfactory cell types. In the VNO, Nav1.2 and Nav1.6 are confined to VSNs, with Nav1.2-immunoreactive somata solely present in the basal layer of the VNO. The subcellular localization of Nav1.3 and Nav1.7 in OSNs can change dramatically during periods of heightened plasticity in the MOE. During the first weeks of development and during regeneration of the olfactory epithelium following chemical lesion, expression of Nav1.3 and Nav1.7 is transiently enhanced in the somata of mature OSNs. Our results demonstrate a highly complex organization of Nav channel expression in the mouse olfactory system, with specific commonalities but also differences between the MOE and the VNO. On the basis of their subcellular localization, Nav1.3 and Nav1.7 should play major roles in action potential propagation in both MOE and VNO, whereas Nav1.2 and Nav1.6 are specific to the function of VSNs. The plasticity of Nav channel expression in OSNs during early development and recovery from injury could reflect important physiological requirements in a variety of activity-dependent mechanisms.

A central mechanism of analgesia in mice and humans lacking the sodium channel NaV1.7

“…Mouse tissue preparation followed previously described methods (Weiss et al, 2011;Bolz et al, 2017). Adult mice (7-9 weeks-ofage) were anaesthetized using a mixture of 165 mg/kg body weight ketamine (Pharmacia GmbH, Berlin) and 11 mg/kg body weight xylazine (Bayer Health Care, Leverkusen), and were transcardially perfused with phosphate-buffered saline (PBS) pH 7.4, followed by 4% (w/v) paraformaldehyde in PBS.…”

A Comparison of the Primary Sensory Neurons Used in Olfaction and Vision

“…This suggests that Nav1.7 is not required for action potential generation but instead is involved in the propagation of the action potential to the synaptic terminal. Other Nav channels including Nav1.3 and Nav1.5 are expressed in OSN and Nav1.3 localizes to the axon suggesting a potential function in action potential generation (Weiss et al, 2011;Bolz et al, 2017). Regardless of the molecular identity of the Nav channels involved, the inward Na + flux further depolarizes the membrane driving the rising phase of the action potential.…”

Slow Inactivation of Sodium Channels Contributes to Short-Term Adaptation in Vomeronasal Sensory Neurons

“…Several Na + channel isoforms have been found to be expressed in VSNs either at mRNA level by RT-PCR or by immunohistochemistry, as follows: Na v 1.1, Na v 1.2, Na v 1.3, Na v 1.6, and Na v 1.7. They differ in level of expression and are localized in different neuronal compartments ( Fieni et al, 2003 ; Rupasinghe et al, 2012 ; Ibarra-Soria et al, 2014 ; Bolz et al, 2017 ). For example, Na v 1.3 and Na v 1.7 are highly expressed and mainly located on axons, while Na v 1.2 and Na v 1.6 were found in the soma of VSNs ( Bolz et al, 2017 ).- Thus, a combination of these Na + channel isoforms and their associated β-subunits is likely to contribute to the Na + currents and the generation of action potentials in VSNs.…”