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

• Published in: Journal of comparative neurology (1911) 2005-05, Vol.486 (2), p.117-131
• Main Authors: Bartoo, Aaron C., Sprunger, Leslie K., Schneider, David A.
• Format: Article
• Language: English
• Subjects: Animals; Axons - metabolism; Axons - ultrastructure; Calcium-Binding Proteins - physiology; Cell Membrane - metabolism; Dendrites - metabolism; Dendrites - ultrastructure; enteric nervous system; Enteric Nervous System - cytology; Enteric Nervous System - metabolism; Ganglia, Autonomic - cytology; Ganglia, Autonomic - metabolism; Gastrointestinal Tract - innervation; Gastrointestinal Tract - physiology; gene expression; guinea pig; Guinea Pigs; Immunohistochemistry; Myenteric Plexus - cytology; Myenteric Plexus - metabolism; NAV1.2 Voltage-Gated Sodium Channel; NAV1.3 Voltage-Gated Sodium Channel; NAV1.6 Voltage-Gated Sodium Channel; NAV1.7 Voltage-Gated Sodium Channel; Nerve Tissue Proteins - genetics; Neurons - cytology; Neurons - metabolism; Protein Subunits - drug effects; Protein Subunits - genetics; RNA, Messenger - metabolism; Sodium Channel Blockers - pharmacology; sodium channels; Sodium Channels - drug effects; Sodium Channels - genetics; Submucous Plexus - cytology; Submucous Plexus - metabolism; Tetrodotoxin - pharmacology
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.20541

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 Nav1.2, Nav1.3, Nav1.6, and Nav1.7 mRNA was detected in small and large intestinal preparations from guinea pigs. Expression of Nav1.1 mRNA as well as Nav1.1‐like immunoreactivity (‐li) were not observed in any intestinal region investigated. Nav1.2‐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. Nav1.3‐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. Nav1.6‐li was primarily observed in the initial axonal segment of colonic myenteric neurons. Nav1.7‐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 Nav1.2‐li cell bodies colocalized with calbindin‐li while colocalization with calretinin‐li was rare. In contrast, 22% of Nav1.3‐li cell bodies colocalized with calretinin‐li but colocalization with calbindin‐li was not observed. In the colon, both Nav1.2‐li and Nav1.3‐li cell bodies frequently colocalized with either calretinin‐li or calbindin‐li. Nav1.2‐li cell bodies also colocalized with the majority of NeuN‐li cells in the small and large intestine. These data suggest that Nav1.1 may not be highly expressed in the ENS, but that Nav1.2, Nav1.3, and Nav1.6, and possibly Nav1.7, have broadly important and distinct functions in the ENS. J. Comp. Neurol. 486:117–131, 2005. © 2005 Wiley‐Liss, Inc.