Voltage-gated sodium channels contribute to the b-wave of the rodent electroretinogram by mediating input to rod bipolar cell GABA_c receptors

Voltage-gated sodium (Na_v) channels are known to augment cone bipolar cell light responses, increasing the electroretinogram (ERG) b-wave in response to stimulus strengths above the cone threshold. However previous invivo studies on a number of animal models have not found a role for Na_v channels in augmenting the b-wave in scotopic conditions below the cone threshold. We recorded ERGs from mice and rats using a series of TTX concentrations and tested retinal output to ensure complete Na_v channel block. We found that TTX concentrations sufficient to completely suppress retinal output caused large (~40%) decrease in the scotopic electroretinogram (ERG) response to high stimulus strengths (1.0logcds/m²). In addition the b-wave was reduced by ~20% even at stimulus strengths that should predominately excite the rod pathway (-2.2logcds/m²). Modulating stimulus strength and background luminance showed that Na_v channel contribution to the b-wave is strongest in mesopic conditions with low strength stimuli. Blocking GABA_c receptors indicted that Na_v channels predominately contribute to the b-wave by supporting GABA_c input to rod bipolar cells in addition to directly amplifying the light response of cone ON bipolar cells. We also determined that saturating levels of TTX reduced the rat b-wave below cone threshold. Na_v channels increase the ERG b-wave in both rod and cone bipolar cell-dominated circuits. In circuits involving rod bipolar cells the effect is mediated indirectly via GABAergic inhibitory cells, while Na_v channels directly located on cone bipolar cells amplify light responses in the cone pathways.