Tetrodotoxin-resistant voltage-gated sodium channels Nav1.8 and Nav1.9 are expressed in the retina

Brendan J. O'Brien, John H. Caldwell, George R. Ehring, Keely M. Bumsted O'Brien, Songjiang Luo, S. Rock Levinson

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Voltage-gated sodium channels (VGSCs) are one of the fundamental building blocks of electrically excitable cells in the nervous system. These channels are responsible for the generation of action potentials that are required for the communication of neuronal signals over long distances within a cell. VGSCs are encoded by a family of nine genes whose products have widely varying biophysical properties. In this study, we have detected the expression of two atypical VGSCs (Nav1.8 and Nav1.9) in the retina. Compared with more common VGSCs, Nav1.8 and Nav1.9 have unusual biophysical and pharmacological properties, including persistent sodium currents and resistance to the canonical sodium channel blocker tetrodotoxin (TTX). Our molecular biological and immunohistochemical data derived from mouse (Mus musculus) retina demonstrate expression of Nav1.8 by retinal amacrine and ganglion cells, whereas Nav1.9 is expressed by photoreceptors and Müller glia. The fact that these channels exist in the central nervous system (CNS) and exhibit robust TTX resistance requires a re-evaluation of prior physiological, pharmacological, and developmental data in the visual system, in which the diversity of VGSCs has been previously underestimated.

Original languageEnglish (US)
Pages (from-to)940-951
Number of pages12
JournalJournal of Comparative Neurology
Volume508
Issue number6
DOIs
StatePublished - Jun 20 2008

Keywords

  • Amacrine cell
  • Photoreceptor
  • Retina
  • Tetrodotoxin
  • Voltage-gated sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)

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    O'Brien, B. J., Caldwell, J. H., Ehring, G. R., Bumsted O'Brien, K. M., Luo, S., & Levinson, S. R. (2008). Tetrodotoxin-resistant voltage-gated sodium channels Nav1.8 and Nav1.9 are expressed in the retina. Journal of Comparative Neurology, 508(6), 940-951. https://doi.org/10.1002/cne.21701