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 (Nav) 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 in vivo studies on a number of animal models have not found a role for Nav 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 Nav 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 (1.0 log cd s/m(2)). In addition the b-wave was reduced by ~20% even at stimulus strengths that should predominately excite the rod pathway (-2.2 log cd s/m(2)). Modulating stimulus strength and background luminance showed that Nav channel contribution to the b-wave is strongest in mesopic conditions with low strength stimuli. Blocking GABAc receptors indicted that Nav channels predominately contribute to the b-wave by supporting GABAc 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. Nav 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 Nav channels directly located on cone bipolar cells amplify light responses in the cone pathways.
Department of Biology, Dalhousie University, 1355 Oxford St., PO Box 15000, Halifax, NS B3H 4R2, Canada. Electronic address: BN948751@dal.ca.
Benjamin J
BJ
Smith
François
F
Tremblay
Patrice D
PD
Côté
D000818:Animals; D004596:Electroretinography / Q000379:methods*; D051379:Mice; D010775:Photic Stimulation / Q000379:methods*; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*
C087200:GABA-C receptor; D018079:Receptors, GABA; D015222:Sodium Channels
(1,2,5,6-Tetrahydropyridin-4-yl) methylphosphinic acid; 6-Cyano-7-nitroquinoxaline-2,3-dion; CNQX; ERG; GABA; GABA(c) receptors; N-Methyl-d-aspartate; NMDA; Na(v); PDA; RBC; TPMPA; TTX; VEP; amacrine cells; bipolar cells; cis-piperidine dicarboxylic acid; electroretinogram; gamma-aminobutyric acid; retina; retinal circuits; rod bipolar cell; sodium channels; tetrodotoxin; visual-evoked potential; voltage-gated sodium channel