Zebrafish Cx55.5(c54x) 'Knock Outs' Have Deficits In Cone-Mediated Vision

Abstract

Purpose: : Cx55.5 hemichannels in the tips of horizontal cell dendrites may function in horizontal cell negative feedback to cone photoreceptors in the zebrafish retina. To test for a link between Cx55.5 hemichannels and the feedback mechanism we investigated: 1) whether Cx55.5 can form hemichannels that are open under physiological conditions, 2) whether the pharmacological profile of Cx55.5 is similar to that of feedback and 3) whether Cx55.5 knock-out fish have visual defects consistent with loss of feedback from HCs to cones.

Results: : 1) Cx55.5 hemichannels are open at physiological membrane potentials and at physiological Ca-concentrations. 2) Hemichannels and feedback are known to be blocked by carbenoxolone, low dose of Co²⁺ and intracellular acidification. Here we show that Cx55.5 hemichannels are also inhibited by HEPES, which may account for the reports of feedback inhibition by HEPES. 3) The retina develops normally in zebrafish lacking Cx55.5 protein but relative to wild type zebrafish, these animals have poorer visual performance as measured with the optokinetic response.

Conclusions: : The data presented in this study show that Cx55.5 is involved in the neural processing in the outer retina. Cx55.5 hemichannels play a role in the feedback mechanism from HCs to cones. This study is the first to demonstrate a change in the visually-guided behavior of an intact living animal by altering the retinal horizontal cell network.

Keywords: horizontal cells • photoreceptors • retina