reduced retinal function in the absence of nav1.6没有nav1.6减少视网膜功能.pdfVIP

Reduced Retinal Function in the Absence of Na 1.6 v 1 ˆ ´ 1,2 Benjamin J. Smith , Patrice D. Cote * 1 Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada, 2 Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada Abstract Background: Mice with a function-blocking mutation in the Scn8a gene that encodes Na 1.6, a voltage-gated sodium v 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 CoCl2 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 s