Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system.

The types of sodium channels that are expressed by neurons shape the rising phase of action potentials and influence patterns of action potential discharge. With regard to the enteric nervous system (ENS), there is uncertainty about which channels are expressed, and in particular it is unknown whether Na(v)1.7 is present. We designed specific probes for the guinea pig Na(v)1.7 alpha subunit as well as for the other tetrodotoxin (TTX)-sensitive alpha subunits (Na(v)1.1, Na(v)1.2, Na(v)1.3, and Na(v)1.6) in order to perform in situ hybridization (ISH) histochemistry on guinea pig myenteric ganglia. We established that only Na(v)1.7 mRNA and Na(v)1.3 mRNA are expressed in these ganglia. The ISH signal for Na(v)1.7 transcripts was found in seemingly all the myenteric neurons. The expression of the Na(v)1.3 alpha subunit was confirmed by immunohistochemistry in a large proportion (62%) of the myenteric neuron population. This population included enteric sensory neurons. Na(v)1.6 immunoreactivity, absent from myenteric neurons, was detected in glial cells only when a high anti-Na(v)1.6 antibody concentration was used. This suggests that the Na(v)1.6 alpha subunit and mRNA are present only at low levels, which is consistent with the fact that no Na(v)1.6 mRNA could be detected in the ENS by ISH. The fact that adult myenteric neurons are endowed with only two TTX-sensitive alpha subunits, namely, Na(v)1.3 and Na(v)1.7, emphasizes the singularity of the ENS. Both these subunits, known to have slow-inactivation kinetics, are well adapted for generating action potentials from slow excitatory postsynaptic potentials, a mode of synaptic transmission that applies to all ENS neuron types.