Contribution of Na v 1.8 sodium channels to retinal function

• Published in: Neuroscience 2017-01, Vol.340, p.279-290
• Main Authors: Smith, Benjamin J, Côté, Patrice D, Tremblay, François
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Aniline Compounds - pharmacology; Animals; Aziridines - pharmacology; Choline - analogs & derivatives; Choline - pharmacology; Cholinergic Antagonists - pharmacology; Electroretinography; Furans - pharmacology; Glycine Agents - pharmacology; Mice, Inbred C57BL; Microelectrodes; NAV1.8 Voltage-Gated Sodium Channel - metabolism; Neurons - drug effects; Neurons - metabolism; Periodicity; Photic Stimulation; Retina - drug effects; Retina - metabolism; Sodium Channel Blockers - pharmacology; Strychnine - pharmacology; Tissue Culture Techniques; Vision, Ocular - drug effects; Vision, Ocular - physiology
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2016.10.054

We examined the contribution of the sodium channel isoform Na 1.8 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 Na 1.8; 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 Na 1.8 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.