Objectives:
Voltage-gated sodium channels (VSGC) are heteromeric protein complexesconsisting of an alpha and two beta subunits. To date, there are 9 alpha
isoforms and these can be differentiated by their sensitivity to the
inhibitor tetrodotoxin (TTX). VSGCs also have distinct expression
patterns in the nervous system, particularly in sub-populations of dorsal
root ganglion sensory fibres. However, little information exists on
their expression in the trigeminal ganglion (TG). VSGCs are important in
action potential propagation but abnormal expression patterns are
observed in various disease conditions including multiple sclerosis and
neuropathic pain. This study characterised the expression of TTX
sensitive Nav1.3, Nav1.6 and Nav1.7 channel subtypes within the TG.
Methods: VSGC subtypes were localised to neuronal sub-populations using
immunocytochemical methods on adult rat TG sections. Sodium channels
were identified using polyclonal antibodies to Nav 1.3, Nav 1.6 or Nav
1.7. Specific neuronal sub-populations were identified by double
labelling of sections with antibodies to NF200, and IB4 for myelinated
A-fibres, non-peptide unmyelinated c-fibres, respectively. Western
blotting confirmed the presence of these three sodium channels in the
TG. Nav1.3 and Nav1.7 distributions were quantified by direct counting
of stained cells.
Results: Nav1.3 was found in 23% of all TG cells. Two different staining patterns
were seen that differentiated small and large cells. Nav1.3 colocalised
with both IB4 (48%) and N52 (47%). Nav 1.7 was found in 56% of all TG
cells, in both myelinated (46%) and unmyelinated cells (49%). Nav1.6
was observed in a few small cells and in some glial-like cells.
Conclusions: These data are the first quantification of this expression in distinct
neuronal sub-populations and should serve as a useful baseline for
studies of sodium channel expression in disease states affecting the
trigeminal nerve.