Tetrodotoxin-resistant voltage-gated sodium channels Na(v)1.8 and Na(v)1.9 are expressed in the retina.
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 (Na(v)1.8 and Na(v)1.9) in the retina. Compared with more common VGSCs, Na(v)1.8 and Na(v)1.9 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 Na(v)1.8 by retinal amacrine and ganglion cells, whereas Na(v)1.9 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.
O'Brien
Brendan J
BJ
Department of Optometry & Vision Science, University of Auckland, Private Bag 92019, Auckland, New Zealand. b.obrien@anu.edu.au
Caldwell
John H
JH
Ehring
George R
GR
Bumsted O'Brien
Keely M
KM
Luo
Songjiang
S
Levinson
S Rock
SR
D025042:Amacrine Cells / Q000378:metabolism; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009457:Neuroglia / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568318:Scn10a protein, mouse; C491885:Scn11a protein, mouse; D015222:Sodium Channels