title: Contribution of Nav1.8 sodium channels to retinal function.
abstract: We examined the contribution of the sodium channel isoform Nav1.8 to retinal function using the specific blocker A803467. We found that A803467 has little influence on the electroretinogram (ERG) a- and b-waves, but significantly reduces the oscillatory potentials (OPs) to 40-60% of their original amplitude, with significant changes in implicit time in the rod-driven range. To date, only two cell types were found in mouse to express Nav1.8; the starburst amacrine cells (SBACs), and a subtype of retinal ganglion cells (RGCs). When we recorded light responses from ganglion cells using a multielectrode array we found significant and opposing changes in two physiological groups of RGCs. ON-sustained cells showed significant decreases while transient ON-OFF cells showed significant increases. The effects on ON-OFF transient cells but not ON-sustained cells disappeared in the presence of an inhibitory cocktail. We have previously shown that RGCs have only a minor contribution to the OPs (Smith et al., 2014), therefore suggesting that SBACs might be a significant contributor to this ERG component. Targeting SBACs with the cholinergic neurotoxin ethylcholine mustard aziridinium (AF64A) caused a reduction in the amplitude of the OPs similar to A803467. Our results, both using the ERG and MEA recordings from RGCs, suggest that Nav1.8 plays a role in modulating specific aspects of the retinal physiology and that SBACs are a fundamental cellular contributor to the OPs in mice, a clear demonstration of the dichotomy between ERG b-wave and OPs.
authors.affiliation: Department of Biology, Dalhousie University, 1355 Oxford St., PO Box 15000, Halifax, NS B3H 4R2, Canada. Electronic address: BN948751@dal.ca.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: Department of Biology, Dalhousie University, 1355 Oxford St., PO Box 15000, Halifax, NS B3H 4R2, Canada; Department of Ophthalmology and Visual Sciences, Dalhousie University, 1276 South Park St., PO Box 15000, Halifax, NS B3H 4R2, Canada. Electronic address: patrice@dal.ca.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Côté
authors.affiliation: Department of Ophthalmology and Visual Sciences, Dalhousie University, 1276 South Park St., PO Box 15000, Halifax, NS B3H 4R2, Canada; Department of Physiology and Biophysics, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, NS B3H 4R2, Canada. Electronic address: ftrembla@dal.ca.
authors.forename: François
authors.initials: F
authors.lastname: Tremblay
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001388:Aziridines / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004596:Electroretinography; D005663:Furans / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010507:Periodicity; D010775:Photic Stimulation; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology*
chemical_list: C520740:A 803467; D000814:Aniline Compounds; D001388:Aziridines; D018680:Cholinergic Antagonists; D005663:Furans; D018684:Glycine Agents; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; D026941:Sodium Channel Blockers; C044894:ethylcholine aziridinium; D013331:Strychnine; D002794:Choline
keywords: Na(v)1.8; electroretinogram; oscillatory potentials; retina; sodium channels; starburst amacrine cells