Expression and distribution of TTX-sensitive sodium channel alpha subunits in the enteric nervous system

The expression and distribution of TTX-sensitive voltage-gated sodium channel (VGSC) alpha subunits in the enteric nervous system (ENS) has not been described. Using RT-PCR, expression of Na(v)1.2, Na(v)1.3, Na(v)1.6, and Na(v)1.7 mRNA was detected in small and large intestinal preparations from guinea pigs. Expression of Na(v)1.1 mRNA as well as Na(v)1.1-like immunoreactivity (-li) were not observed in any intestinal region investigated. Na(v)1.2-li was primarily observed within the soma of the majority of myenteric and submucosal neurons, although faint immunoreactivity was occasionally observed in ganglionic and internodal fibers. Na(v)1.3-li was observed in dendrites, soma, and axons in a small group of myenteric neurons, as well as in numerous myenteric internodal fibers; immunoreactivity was rarely observed in the submucosal plexus. Na(v)1.6-li was primarily observed in the initial axonal segment of colonic myenteric neurons. Na(v)1.7-li was observed in dorsal root ganglia neurons but not in the myenteric plexus of the small and large intestine. In the ileum, 37% of Na(v)1.2-li cell bodies colocalized with calbindin-li while colocalization with calretinin-li was rare. In contrast, 22% of Na(v)1.3-li cell bodies colocalized with calretinin-li but colocalization with calbindin-li was not observed. In the colon, both Na(v)1.2-li and Na(v)1.3-li cell bodies frequently colocalized with either calretinin-li or calbindin-li. Na(v)1.2-li cell bodies also colocalized with the majority of NeuN-li cells in the small and large intestine. These data suggest that Na(v)1.1 may not be highly expressed in the ENS, but that Na(v)1.2, Na(v)1.3, and Na(v)1.6, and possibly Na(v)1.7, have broadly important and distinct functions in the ENS.