title: Physiological maturation of photoreceptors depends on the voltage-gated sodium channel NaV1.6 (Scn8a).
abstract: Voltage-gated sodium channels (VGSCs) ensure the saltatory propagation of action potentials along axons by acting as signal amplifiers at the nodes of Ranvier. In the retina, activity mediated by VGSCs is important for the refinement of the retinotectal map. Here, we conducted a full-field electroretinogram (ERG) study on mice null for the sodium channel NaV1.6. Interestingly, the light-activated hyperpolarization of photoreceptor cells (the a-wave) and the major "downstream" components of the ERG, the b-wave and the oscillatory potentials, are markedly reduced and delayed in these mice. The functional deficit was not associated with any morphological abnormality. We demonstrate that Scn8a is expressed in the ganglion and inner nuclear layers and at low levels in the outer nuclear layer beginning shortly before the observed ERG deficit. Together, our data reveal a previously unappreciated role for VGSCs in the physiological maturation of photoreceptors.
authors.affiliation: Molecular Medicine Program, Ottawa Health Research Institute, and University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Côté
authors.forename: Yves
authors.initials: Y
authors.lastname: De Repentigny
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Coupland
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwab
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Roux
authors.forename: S Rock
authors.initials: SR
authors.lastname: Levinson
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kothary
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004307:Dose-Response Relationship, Radiation; D004596:Electroretinography / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D010786:Photoreceptor Cells / Q000254:growth & development / Q000502:physiology* / Q000528:radiation effects / Q000648:ultrastructure; D015222:Sodium Channels / Q000172:deficiency / Q000502:physiology*
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels