Contribution of Nav1.8 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: electroretinogram; Nav1.8; oscillatory potentials; retina; sodium channels; starburst amacrine cells
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2016.10.054

[Display omitted] •Sodium channel isoform Nav1.8 contributions to retinal function were studied using the specific blocker A803467.•A803467 had no effect on ERG a- and b-waves, but significantly reduced the oscillatory potentials (OPs).•Targeting starburst amacrine cells (SBACs) with the cholinergic neurotoxin AF64A reduced OPs similar to A803467.•A803467 affect ON-sustained retinal ganglion cells (RGCs) directly and ON/OFF transient though inhibitory circuits.•SBACs, through Nav1.8 modulation, selectively amplify/propagate OPs; Nav1.8 modulates specific aspects of RGC physiology. 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.