Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
PLoS One. 2012;7(2):e31476. doi: 10.1371/journal.pone.0031476. Epub 2012 Feb 15.
Mice with a function-blocking mutation in the Scn8a gene that encodes Na(v)1.6, a voltage-gated sodium channel (VGSC) isoform normally found in several types of retinal neurons, have previously been found to display a profoundly abnormal dark adapted flash electroretinogram. However the retinal function of these mice in light adapted conditions has not been studied.
METHODOLOGY/PRINCIPAL FINDINGS: In the present report we reveal that during light adaptation these animals are shown to have electroretinograms with significant decreases in the amplitude of the a- and b-waves. The percent decrease in the a- and b-waves substantially exceeds the acute effect of VGSC block by tetrodotoxin in control littermates. Intravitreal injection of CoCl(2) or CNQX to isolate the a-wave contributions of the photoreceptors in littermates revealed that at high background luminance the cone-isolated component of the a-wave is of the same amplitude as the a-wave of mutants.
CONCLUSIONS/SIGNIFICANCE: Our results indicate that Scn8a mutant mice have reduced function in both rod and the cone retinal pathways. The extent of the reduction in the cone pathway, as quantified using the ERG b-wave, exceeds the reduction seen in control littermates after application of TTX, suggesting that a defect in cone photoreceptors contributes to the reduction. Unless the postreceptoral component of the a-wave is increased in Scn8a mutant mice, the reduction in the b-wave is larger than can be accounted for by reduced photoreceptor function alone. Our data suggests that the reduction in the light adapted ERG of Scn8a mutant mice is caused by a combination of reduced cone photoreceptor function and reduced depolarization of cone ON bipolar cells. This raises the possibility that Na(v)1.6 augments signaling in cone bipolar cells.
先前研究发现，编码电压门控钠离子通道（VGSC）亚型 Na(v)1.6 的 Scn8a 基因突变的小鼠，其暗适应闪光视网膜电图表现出严重异常。然而，这些小鼠在明适应条件下的视网膜功能尚未得到研究。
方法/主要发现：在本报告中，我们揭示了这些动物在明适应条件下的视网膜电图显示出 a 波和 b 波幅度显著降低。a 波和 b 波的百分降低量大大超过了对照同窝仔鼠中 VGSC 阻断剂河豚毒素的急性作用。在同窝仔鼠中，通过玻璃体内注射 CoCl(2)或 CNQX 来分离光感受器的 a 波贡献，发现高背景亮度下，锥体分离的 a 波成分与突变体的 a 波幅度相同。
结论/意义：我们的结果表明，Scn8a 突变小鼠的 rod 和 cone 视网膜通路功能均降低。使用 ERG b 波定量的 cone 通路减少程度超过了 TTX 应用后对照同窝仔鼠中观察到的减少程度，表明 cone 光感受器的缺陷导致了减少。除非突变体小鼠的 a 波的 postreceptoral 成分增加，否则 b 波的减少量大于仅由光感受器功能降低所解释的范围。我们的数据表明，Scn8a 突变小鼠明适应 ERG 的减少是由 cone 光感受器功能降低和 cone ON 双极细胞去极化减少共同引起的。这提出了 Na(v)1.6 增强 cone 双极细胞信号传递的可能性。
