Depleted A–Wave in Scn8a–Null Mice: Requirement for a Voltage–Gated Sodium Channel in the Maturation of the Outer Retina

Abstract

Abstract: : Purpose:To determine the effects of genetic ablation of Scn8a (Nav1.6), a widely expressed 'brain–type' voltage–gated sodium channel (VGSC), on retinal function. Methods:A full field ERG study was performed on dark–adapted post–natal day 16 mice from two lines harbouring distinct 'null' mutations in Scn8a. Results:This study revealed that in Scn8a–null mice, the activation of the light–induced hyperpolarization of photoreceptor cells (the a–wave) is markedly reduced and 'downstream' components of the ERG (the b–wave and its subcomponent, the oscillatory potentials) are virtually extinguished. All components of the ERG are also significantly delayed. VGSCs are fundamental to the propagation of action potentials in excitable tissues. This result is surprising however since photoreceptors rely on graded potentials to convey information to neural elements in the inner nuclear layer. Furthermore, a histopathological, ultrastructural and cellular contribution survey failed to reveal degenerative or developmental retinal abnormalities. Vascularization of the Scn8a–null retina is also normal, indicating that hypoxia is unlikely to be the underlying cause of the functional defect. Conclusions:VGSCs appear to be playing a role in photoreceptor development. Possible direct and indirect pathways are discussed.

Keywords: electroretinography: non-clinical • retinal development • photoreceptors