Molecular Identities of Two Tetrodotoxin-Resistant Sodium Channels in Corneal Axons

Abstract

Previous electrophysiological studies have demonstrated that tetrodotoxin-resistant (TTX-R) sodium channels contribute to action potential electrogenesis and conduction along non-myelinated PNS axons. Moreover, recent work has established that TTX-R sodium channels play a major role in the generation of action potentials in the terminals of non-myelinated nociceptive axons innervating the cornea. We have utilized subtype-specific antibodies to sodium channels Nav1.8 and Nav1.9 to examine the molecular identity of the TTX-R sodium channels that are present in these axons. Both Nav1.8 and Nav1.9 sodium channels are expressed diffusely along the entire lengths of non-myelinated corneal axons, from the nerve plexus at the corneoscleral limbus to the distal corneal leash fibers. Moreover, both Nav1.8 and Nav1.9 are localized at the bulb-like nerve terminals of the leash fibers within the superficial epithelial layers of the cornea. These observations suggest that both TTX-R sodium channels Nav1.8 and Nav1.9 contribute to the electrogenesis of non-myelinated axons of the cornea.